Структурно-функциональная характеристика системы рестрикции-модификации ДНК CfrBI штамма Cirobacter freundii 4111 тема диссертации и автореферата по ВАК РФ 03.00.03, кандидат биологических наук Белецкая, Ирина Викторовна

• Белецкая, Ирина Викторовна
• кандидат биологических наук
• 2002

Оглавление диссертации кандидат биологических наук Белецкая, Ирина Викторовна

ВВЕДЕНИЕ.

I. ОБЗОР ЛИТЕРАТУРЫ.

1.1. Системы рестрикции-модификации.

1.1.1. Явление рестрикции-модификации.

1.1.2. Сайт-специфические эндонуклеазы и ДНК-метилтрансферазы.

1.1.3. Распространение систем рестрикции-модификации.

1.1.4. Молекулярная организация систем рестрикции-модификации.

1.1.5. Классификация ферментов системы рестрикции-модификации.

1.1.6. Системы рестрикции-модификации I типа.

1.1.7. Системы рестрикции-модификации 11/2 типа.

1.1.8. Системы рестрикции-модификации II типа.

1.1.9. Ферменты системы рестрикции-модификации III типа.

1.1.10. Ферменты системы рестрикции-модификации IV типа.

1.2. Непарные ДНК-метилтрансферазы и эндонуклеазы рестрикции.

1.3. Метилирование ДНК в E.coli.

1.3.1. Dam-зависимая регуляция генной экспрессии.

1.4. Метилирование ДНК эукариотических организмов.

1.4.1. Метилирование и процессы развития.

1.4.1.1. Импринтинг.

1.4.1.2. Инактивации хромосомы X.

1.4.2. Распределение CpG в геноме человека.

1.4.3. Влияние метилирования ДНК на структуру хроматина.

1.5. Регуляция экспрессии генов в системах Р-М.

1.5.2. Регуляция экспрессии генов Llal системы Р-М из Lactococcus lactus.

1.5.3. Регуляция экспрессии генов в системах Р-М II типа.

1.5.4. Регуляция экспрессии генов Р-М систем III типа.

II. МАТЕРИАЛЫ И МЕТОДЫ ИССЛЕДОВАНИЙ.

11.1. Материалы.

11.1.1. Штаммы бактерий, бактериофаги, фаговые и плазмидные вектора.

11.1.2. Среды и основные буферы.

11.1.3. Материалы и реактивы.

11.2. Методы исследования.

11.2.1. Выделение плазмидной ДНК.

11.2.1.1. Лизис щелочью.

11.2.1.2. Модифицированный метод лизис щелочью с последующей очисткой ДНК.

11.2.1.3. Лизис кипячением.

11.2.1.4. Очистка плазмидной ДНК равновесным центрифугированием в градиенте хлористого цезия.

11.2.2. Получение компетентных клеток Е. coli и их трансформация.

11.2.3. Полимеразная цепная реакция (ПНР).

11.2.4. Препаративное выделение фрагментов ДНК из легкоплавкой агарозы.

11.2.5. Препаративное выделение фрагментов ДНК из полиакриламидных гелей.

11.2.6. Получение препаратов фагов Xvir и q>80v/r в высоком титре.

11.2.7. Выделение ДНК фагов Ш857, Xvir и q>80v/r.

11.2.8. Определение ферментативной активности и специфичности R.C/rBI.

11.2.9. Определение точки разрезания фосфодиэфирной связи R.C/rBI на молекуле субстратной ДНК.

11.2.10. Клонирование гена эндонуклеазы R.C/rBI.

11.2.11. Клонирование гена ДНК-метилтрансферазы М CfrBL.

11.2.12. Экспрессия генов эндонуклеазы His6-R.CyrBI- и метилтрансферазы His6-M.QrBI.

11.2.13. Определение молекулярного веса белков R'C/rBI и M'CJrBI.

11.2.15. Определение оптимальных условий реакции для метилтрансферазы His6-C/rBI.

11.2.16. Реакция метилирования in vivo и in vitro.

11.2.17. Определение типа цитозинового метилирования, осуществляемое M.CfrBl.

II.2.18. Конструирование рекомбинантиых плазм ид с перекрывающимися уникальными сайтами для определения позиции метилированного цитозина в последовательности сайта CfrBl.

11.2.19. Конструирование плазмид, производных pFD51, содержащих различные варианты промоторных областей генов cfrBIR and cfrBIM.

11.2.20. Определение активности галактокиназы.

11.2.21. Определение связывания Ш.С/гШ с промоторной областью гена cfrBIM методом задержки в агарозном геле.

11.2.22. Транскрипция in vitro.

11.2.23. Определение нуклеотидной последовательности ДНК.

III. РЕЗУЛЬТАТЫ И ОБСУЖДЕНИЕ.

111.1. Характеристика генетической организации системы рестрикции-модификации CfrBl.

111.2. Сравнительный анализ аминокислотных последовательностей Ш.С/гШ и R.C/rBI с последовательностями других ферментов систем Р-М.

111.3. Определение сайта узнавания и места гидролиза фосфодиэфирной связи на молекулах субстратной ДНК R.C^rBI.

111.4. Определение типа метилирования цитозиновых остатков, осуществляемое Ш.С/гШ.

111.5. Создание штаммов-продуцентов с регулируемым уровнем экспрессии ферментов системы рестрикции-модификации CfrB1.

111.5.1. Клонирование и экспрессия гена cfrBIR.

111.5.2. Клонирование и экспрессия гена cfrBIM.

111.6. Очистка и определение оптимальных условий реакции для His6-M.C/>BI.

111.7. Определение локализации метилированного основания в последовательности сайта CfrBl.

111.8. Исследование регуляции экспрессии генов в системе рестрикции-модификации CfrBI.

111.8.1. Определение минимального района ДНК с функционально активным промотором гена cfrBIM.

111.8.2. Изучение регуляции генов cfrBIM и cfrBIR в системе in vivo.

111.8.3. Зависимость эффективности транскрипции с промоторов генов cfrBIR и cfrBIM от метилирования цитозинов в сайте CfrBl, расположенного в промоторной зоне этих генов.

111.8.4. Транскрипция in vitro с промоторов генов cfrBIR и cfrBIM.

111.8.5. Новый способ регуляции генной активности систем R-M.

ВЫВОДЫ.

Введение диссертации (часть автореферата) на тему «Структурно-функциональная характеристика системы рестрикции-модификации ДНК CfrBI штамма Cirobacter freundii 4111»

Системы рестрикции - модификации (Р-М) широко распространены среди различных микроорганизмов. К настоящему времени обнаружено и охарактеризовано свыше 3000 различных систем Р-М с более чем 200 специфичностями (Roberts and Macelis, 1998). Основная функция систем Р-М II типа, компонентами которой являются эндонуклеазы рестрикции (ЭР) и модифицирующие ДНК-метилтрансферазы (МТ), сводятся к защите бактериальной клетки-хозяина от проникновения чужеродной ДНК. Имеются также данные о том, что ферменты рестрикции и модификации могут оказывать влияние на такие важнейшие клеточные процессы, как репликация, транскрипция, транспозиция и рекомбинация.

ЭР и МТ широко используют в качестве инструментов в генно-инженерных работах при получении рекомбинантных ДНК в биологии, в медицине и в сельскохозяйственной биотехнологии. Это, в первую очередь, определяет актуальность прикладного аспекта изучения систем Р-М, заключающегося в поиске штаммов с новыми специфичностями, в получении высокоэффективных продуцентов ферментов.

Ферменты систем Р-М являются также привлекательной моделью для изучения белок-нуклеинового и белок-белкового взаимодействия, благодаря широкому разнообразию последовательностей узнаваемой ДНК, высокой специфичности ферментов и тому обстоятельству, что для многих из них известны аминокислотные последовательности и для более чем 15 белков сделан рентгеноструктурный анализ. В последнее время системы Р-М все больше привлекают исследователей с точки зрения изучения регуляции экспрессии генов. Продукты генов системы - МТ и ЭР - являются белками, составляющими защитную систему клетки, регуляция экспрессии их генов важна для выживания хозяйского организма. Основной смысл регуляции активностей генов в системах Р-М - предотвращение авторестрикции, т.е. клеточная ДНК должна быть полностью модифицирована к моменту появления эндонуклеазной активности. Поскольку многие гены систем Р-М локализованы на плазмидах, генная регуляция важна не только для предотвращения фрагментации ДНК хозяйского организма, но и для проникновения и установления системы Р-М в новой клетке-хозяине. Механизмы регуляции активности генов в системах Р-М различны и требуют детального изучения для каждой из систем. Объектом нашего исследования является система Р-М С/гШ, обнаруженная на природной плазмиде в штамме Citrobacter freundii 4111. Гены системы R-M CfrBl расположены дивергентно и их промоторные области в значительной степени перекрываются. Уникальный для всей последовательности генов сайт CfrBl локализован в межгенной области. Перекрывание промоторных областей генов и расположение уникального сайта CfrBl в этой области перекрывания делает эту систему привлекательной моделью для исследования регуляции экспрессии генов.

Настоящая диссертационная работа посвящена исследованию структурно-функциональной организации системы рестрикции-модификации CfrBl, характеристике специфичности ферментов, кодируемых генами этой системой, и изучению механизма регуляции экспрессии генов cfrBIM и cfrBIR. Исходя из этого, в работе последовательно решались следующие задачи:

1. Идентифицировать генетические детерминанты системы Р-М CfrBl, обнаруженной на природной плазмиде клинического штамма Citrobacter freundii.

2. Клонировать гены cfrBIM и cfrBIR и определить их нуклеотидные последовательности. Охарактеризовать генетическую организацию системы Р-М CfrBl.

3. Сконструировать штаммы с увеличенным синтезом ферментов системы, для получения высокоактивных и гомогенных препаратов МТ и ЭР.

4. Определить последовательность узнавания и место гидролиза фосфодиэфирной связи для R.C/rBI.

5. Определить тип модификации, осуществляемый M.C/rBI, и положение цитозинового основания в сайте CfrBl, подвергающегося метилированию.

6. Изучить механизм регуляции экспрессии генов системы Р-М CfrBl.

Работа выполнена в ВНТК "Генная активность" Института биохимии и физиологии микроорганизмов РАН.

I. ОБЗОР ЛИТЕРАТУРЫ

Заключение диссертации по теме «Молекулярная биология», Белецкая, Ирина Викторовна

выводы

1. Определена первичная структура генов системы рестрикции-модификации CfrBl и установлено, что гены системы расположены дивергентно относительно друг друга. В области перекрывания промоторов генов cfrBIM и cfrBIR расположен уникальный для всей последовательности системы рестрикции-модификации сайт CfrBl.

2. Сконструированы штаммы-продуценты эндонуклеазы рестрикции CfrBl и ДНК-метилтрансферазы CfrBl. Разработана схема очистки гомогенного препарата фермента ДНК-метилтрансферазы CfrBl.

3. Определен сайт узнавания и место гидролиза фосфодиэфирной связи эндонуклеазы рестрикции CfrBl. Показано, что метилтрансфераза CfrBl относится к классу N4-цитозиновых метилтрансфераз и метилирует наружный цитозин в последовательности 5'-4mCCWWGG -3'.

4. Предложена и экспериментально подтверждена новая модель регуляции экспрессии генов систем рестрикции-модификации. Впервые показано участие N4mC остатков ДНК в регуляции экспрессии генов на уровне транскрипции.

Список литературы диссертационного исследования кандидат биологических наук Белецкая, Ирина Викторовна, 2002 год

1. Бурьянов, Я.И., Ерошина, Н.В., Вагабова, JI.M., Ильин, А.В. О нахождении 6-метиламинопурина в ДНК пыльце высших растений. // Докл. АН СССР. 1972. 206, 982994.

2. Ванюшин, Б.Ф., Кадырова, Д.Х., Каримов, Х.Х., Белозерский, А.Н. Минорные основания в ДНК высших растений.//Биохимия. 1971. 36, 1251-1258.

3. Ванюшин, Б.Ф., Бердышев, Г.Д. Молекулярно-генетические механизмы старения, Медицина, Москва, 1977.

4. Зайцев, Е.Н., Зайцева, Е.М., Бакланова, И.В., Горелов, В.Н., Кузьмин, Н.П., Крюков, В.М., Ланцов, В.А. Клонирование и секвенирование гена гесА из штамма Pseudomonas aeruginosa. II Генетика. 1986. Т. 22. С. 2721-2727.

5. Кравец, А.Н., Солонин, А.С., Захарова, М.В.и Тарутина, З.Е. 1992. Плазмидная локализация и клонирование генов системы рестрикции-модификации из штамма Citrobacter freundii 4111. Мол.генет.микробиол.вирусол., 7-8, 4-7.

6. Лихтенштейн, А.В., Киселева, Н.П. Метилирование ДНК и канцерогенез.// Биохимия, 2001, 66,293-316.

7. Мазин, А.Л., Ванюшин, Б.Ф. Потеря динуклеотидов CpG из ДНК. II. Метилированные и неметилированные гены позвоночных.// Мол.биол., 1987, 21,552-562.

8. Мазин, А.Л., Ванюшин, Б.Ф. Потеря динуклеотидов CpG из ДНК. I.Метилированные и неметилированные компартаменты генома у эукариот с различным содержанием 5-метилцитозина в ДНК.// Мол.биол., 1987, 21,543-551.

9. Нестеренко, В.Ф., Бурьянов, Я.И., Баев А.А. Выделение и свойства ДНК-цитозин-метилазы из Escherichia coli MRE 600. // Биохимия. 1979. Т. 44. С. 130-141.

10. Никольская, И.И., Карпец, Л.З., Карташева, И.М., Лопатина, Н.Г.,Скрипкин, Е.А., Сучков, С.А., Упорова, Т.М., Грубер, И.М., Дебов, С.С. Ферменты новой системы с хозяйской специфичностью &о47П. // Мол. генет. микробиол. вирусол. 1983. 12, 5-10.

11. Пятрушите, М.П., Битинайте Ю.Б., Керсулите, Д.Р., Менкевичус, С.Ю., Буткус, В.В., Янулайтис, А.А. Новый тип эндонуклеаз рестрикции. // Докл. АН СССР. 1987. 295. 1250-1253.

12. Янулайтис, А.А., Стакенас, П.С., Пятрушите, М.П., Битинайте, Ю.Б., Климашаускас, С.Й., Буткус, В.В. Изучение специфичности новых рестриктаз и метилаз. Необычная модификация цитозина по 4-ому положению // Молекул, биология. 1984. Т. 18. С. 115-129.

13. Abadjieva, A., Patel, J., Zinkevich,V. and Firman, К. Deletions within the DNA recognition subunit of M.EcoR.1241 that identify a region involved in protein-protein interactions between HsdS and HsdM.// J.Mol.Biol. 1994. 241, 35-43.

14. Adams, R.L., McKay, E.L., Craig, L.M.and Burdon, R.H. Methylation of mosquito DNA. // Biochim. Biophys. Acta. 1979. 563, 72-81.

15. Adams, G.M. and Blumenthal, R.M. Gene /mJIW: a possible modulator of Pvull endonuclease subunit association.// Gene. 1995.157:193-199.

16. Aggarwal, A.K. Structure and function of restriction endonucleases.// Curr. Opin. Struct.Biol. 1995, 5,11-19.

17. Ahmad, I., Krishnamurthy, V., Rao, D.N. DNA recognition by the £coP15I and Eco?l modificationmethyltransferases. //Gene. 1995. V. 157. P. 143-147.

18. Ahmad, I. and Rao, D.N. Interaction of £coP15I DNA methyltransferase with oligonucleotides containing the asymmetric sequence 5'-CAGCAG-3'. // J. Mol. Biol. 1994. 242, 378-388.

19. Ahmad, I. and Rao, D.N. Photolabeling of the Eco? 15 DNA methyltransferase with S-adenosyl-L-methionine. // Gene. 1994. 142,67-71.

20. Ahmad, Land Rao, D.N. Functional analysis of conserved motifs in Eco?\5l DNA methyltransferase. // J. Mol. Biol. 1996. 259,229-240.

21. Altschul, S.F, Madden, T.L., Schaffer, A.A., Zhang, J., Zhang, Z., Miller, W., Lipman, D.J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.// Nucleic Acids Res. 1997. 25: 3389-3402.

22. Alvarez, M.A., Chater, K.F., Rodicio, M.R. Complex transcription of an operon encoding the Sail restriction-modification system of Streptomyces albus G.ll Mol.Microbiol., 1993,8, 243252.

23. Alvarez, M.A., Gomes, A., Gomes, P., Rodicio, M.R. Expression of the Sail restriction-modification system of Streptomyces albus G in Escherichia coli./f Gene, 1995,157,231 -232

24. Alvarez, M.A., Gomes, A., Gomes, P., Brooks, J.E., Rodicio, M.R. Comparative analysis of expression of the Sail restriction-modification system in Escherichia coli and Streptomyces.il Mol.Gen.Genet., 1996,253,74-80.

25. Anteguera, F.and Bird, A. Number of CpG islands and genes in human and mouse.// Proc.Natl. Acad.Sci.USA, 1993, 90,11995-11999.

26. Anton, B.P., Heiter,D.F., Benner, J.S., Hess, E.J., Greenough,.L, Moran, L.S., Statko, B.E. and Brooks, J. Cloning and characterization of the Bglll restriction-modification system reveals a possible evolutionary footprint.// Gene. 1997.187, 19-27.

27. Arber, W. and Dussoix, D. Host specificity of DNA produced by Escherichia coli: I. Host controlled modification of bacteriophage lambda.// J.Mol.Biol., 1962,5,18-36.

28. Arber W., Morse M.L. Host-specificity of DNA produced by Escherichia coli. VI. Effects on bacterial conjugation. // Genetics. 1965. V. 51. P. 137-148.

29. Arber, W. and Wauters-Willems, D. Host specificity of DNA produced by Escherichia coli: XII. The two restriction and modification systems of strain 15T.// Mol.Gen.Genet., 1970, 108,203-217.

30. Arber, W., Yuan, R. and Bickle, T.A. Strain-specific modification and restriction of DNA in bacteria.// In: F.Antoni and A.Farago (ed.), Post synthetic modification of macromolecules.// Elsevier Science Publishing, Inc., New York, 1974,3-22.

31. Ausubel, F.M., Brent, R., Kingston, R.E., Moore, D.D., Sedman, J.G., Smith, J.A.and Struhl, K. In: Wiley J. and Sons (Eds.) Current protocols in molecular biology. // New York. V. 1.1995.

32. Bachi В., Reiser J., Pirrotta V. Methylation and cleavage sequences of the EcoPl restriction-modification enzyme. //J. Mol. Biol. 1979. 128, 143-163.

33. De Backer O.and Colson C. Identification of the recognition sequence for the M'SYyLTI methyltransferase of Salmonella typhimurium LT7: an asymmetric site typical of type-Ill enzymes. // Gene. 1991. 97,103-107.

34. De Backer O.and Colson C. Two-step cloning and expression in Escherichia coli of the DNA restriction-modification system S^LTI of Salmonella typhimurium. II J. Bacteriol. 1991. 173, 1321-1327.

35. Barcus, V.A., Titheradge, A.J.B. and Murray, N.E. The diversity of alleles at the hsd locus in natural populations of Escherichia coli.ll Genetics. 1995. 140,1187-1197.

36. Barras, F. and Marinus, M.G. The great GATC: DNA methylation in E.coli.11 Trends in Genet. 1989. 5,139-143.

37. Baxter, В. K., and Topal, M. D. Formation of a cleavasome: enhancer DNA-2 stabilizes an active conformation of Nael dimer // Biochemistry. 1993. 32, 8291-8298.

38. Baylin, S.B., Hopener, J.W., de Bustros, A., Steenbergh, P.H., Lips, C.J. andNelkin,B.D. DNA methylation patterns of the calcitonin gene in human lung cancers and lymphomas.// Cancer Res. 1986,46,2917-2922.

39. Baylin, S.B., Fearon, E.R. and Vogelstein, B. Hypermethylation of the 5' region of the calcitonin gene is a property of human lymphoid and acute myeloid malignancies DNA.// Blood . 1987, 70,412-417.

40. Baylin, S.B., Herrman, J.G., Graff, J.R., Vertino, P.M. and Issa,J .-P. Alterations in DNA methylation: a fundamental aspect of neoplasia.// Adv.Cancer Res. 1998. 72,141-196.

41. Beletskaya, I.V., Zakharova, M.V., Shlyapnikov, M.G., Semenova, L.M., Solonin, A.S. DNA methylation at the CfrBl site is involved in expression control in the CfrBl restriction-modification system.//Nucleic Acids Res. 2000.28, 3818-3822.

42. Berge, Т., Ellis, D.J., Dryden, D.T.F., Edwardson, J.M. and Henderson, R.M. Translocation-independent dimerization of the Есо¥Л endonuclease visualized by atomic force microscopy.// Biophysical Journal. 2000. 79,479-484.

43. Bertani, G. and Weigle, J.J. Host controlledvariation in bacterial viruses.// J.Bacteriol, 1953. 65, 113-121.

44. Bestor, Т.Н., Laudano, A.P., Mattaciano, R. and Ingram, V.M. Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA.// J.Mol.Biol. 1983. 203, 971-983.

45. Bestor, Т.Н., DNA methylation: evolution of a bacterial immune function into a regulator of gene expression and genome structure in higher eukaryotes.// Philos.Trans. Roy.Soc. (London). 1990, 326,179-187.

46. Betlach, M., Hershfield, V., Chow, L., Brown, W., Goodman, H.M., and Boyer, H.W. A restriction endonuclease analysis of the bacterial plasmid controlling the EcoRI restriction and modification of DNA.// Fed. Proc. 1976. 35, 2037-43.

47. Bickle, T.A. The ATP depended restriction endonucleases. In: S.M.Linn and R J.Roberts (Eds.) Nucleases. // Cold Spring Harbor Laboratory. Cold Spring Harbor. New York. 1982. 85-108.

48. Bickle, T.A. Macroevolution by transposition: drastic modification of DNA recognition by a type I restriction enzyme following Tn5 transposition.// EMBO J. 1993. 12, 4585-4591.

49. Bilcock, D.T. and Halford, S.E. DNA restriction dependent on two recognition sites: activities of the Sfil restriction-modification system in Escherichia coli.ll Mol. Microbiol. 1999. 31,1243-1254.

50. Bilcock, D.T., Daniels, L.E., Bath, A.J. and Halford, S.E. Reactions of type II restriction endonucleases with 8-base pair recognition sites.// The Journal of Biological chemistry. 1999. 274,36379-36385.

51. Bird, A.P. CpG-rich islands and the function of DNA methylation.// Nature. 1986. 321, 209-213.

52. Bist, P., Sistla, S., Krishnamurthy, V., Acharya, A., Chandrakala, В., Rao, D.N. S-adenosyl-L-methionine is required for DNA cleavage by type III restriction enzymes. J Mol Biol. 2001.310,93-109.

53. Boer, H.W. and Roulland-Dussoix, D. A complementation analysis of the restriction and modification of DNA in Escherichia coli.11 J.Mol.Biol. 1969, 41, 459-472.

54. Bolker, M., Kahmann, R. The E.coli regulatory protein OxyR discriminates between methylated and unmethylated states of the phage Mu mom promoter.// The EMBO J., 1989. 8, 2403-2410.

55. Bougueleret, L., Schwarzstein, M, Tzugita, A. and Zabeau, M. Characterization of the genes coding for the EcoRV restriction and modification system of Escherichia coli.ll Nucleic Acids Res. 19 12, 3659-3676.

56. Braaten, В., Nou, X., Kaltenbach, L. and Low, D. Methylation patterns in pap regulatory DNA control pyelonephritis-associated pili phase variation in E. coli. Cell. 1994. 76, 577-588.

57. Braun R.E. and Wright, A. Dna methylation differetially enchances the expression of one of the two E.coli dnaA promoters in vivo and in vitro Л Mol.Gen.Genet. 1986. 202, 246-250.

58. Brinkley P., Bautista D.S., Graham F.L. The cleavage site of restriction endonuclease Mnll. И Gene. 1991.100,267-268.

59. Brown, N.L. and Smith, M. A general method for defining restriction enzyme-cleavage and recognition sites.// Methods Enzymol. 1980. 65, 391-404.

60. Bujnicki, J.M., Radlinska, M. Molecular evolution of DNA- (cytozine-N4) methyltransferases:evidence for their polyphyletic origin.//Nucleic Acids Research. 1999. 27, 4501-4509.

61. Bullas, L.R., Colson, C. and Neufeld, B. Deoxyribonucleic asid restriction and modification system in Salmonella-, chromosomally located systems of different serotypes.// J.Bacteriol. 1980,141,275-292.

62. Busby S., Kolb A., Minchin, S. DNA-protein interaction: principles and protocols.// Methods in molecular biology, ed. by G. Geoff Kneale. Humana press Inc., Ottowa, New Jersey. 1994.30.397-411.

63. Casdesus, J. and Torreblanca, J. In: Epigenetic Mechanisms of Gene Regulation.// eds. Russo, V.E.A., Martienssen,R.A. and Riggs,A.D. Cold Spring Harbor Lab. Press, Plainvview, NY, 1996.141-153.

64. Cezarini, G., Muesing, A.M. and Polisky, B. Control of ColEl DNA replication: the гор gene product negatively affects transcription from the replication primer promoter.// Proc Natl Acad Sci USA. 1982. 79,6313-6317.

65. Chadrasegaran, S., Lunnen, K.D., Smith, H.O. and Wilson, G.G. Cloning and seguencing the Hinfi restriction and modification genes.// Gene. 1988. 70, 387-382.

66. Chater K.F., Wilde L.C. Streptomyces albus G mutants defective in the SalGl restriction-modification system. // J. Gen. Microbiol. 1980. 116, 323-334.

67. Chen, R.Z., Pettersson, U., Beard, C., Jackson-Grusby, L. and Jaenisch, R. Mutations and epimutations in mammalian cells.// Nature. 1998. 395,89-93.

68. Cheng, X., Balendiran, K., Schildkraut, I. and Anderson, J.E. Structure of Pvull endonuclease with cognate DNA.// EMBO J. 1994. 13, 3927-3935.

69. Christofori, G. and Semb, H. The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene.// Trends Biochem.Sci., 1999. 24,73-76.

70. Colson C. Genetics of R-M systems in Salmonella. II Heredity. 1978. 41,123.

71. Coligan, J. E., Dunn, В. M., Ploegh, H. L., Speicher, D. W., and Wingfield, P.T. In: Wiley J. and Sons. (Eds.) Current protocols in protein science. // New York. V. 1. 1995.

72. Conrad, M. and Topal, M. D. Modified DNA fragments activate Nael cleavage of refractory DNA sites //Nucleic Acids Res. 1992. 20, 5127-5130.

73. Dartois V., De Backer O., Colson C. Sequence of the Salmonella typhimurium StyLTI restriction-modification genes: homologies with Eco?\ and Eco?\5 type-Ill R-M systems and presence of helicase domains. // Gene. 1993.127,105-110.

74. Davies, G.P., Powell, L.M., Webb, J.L., Cooper, L.P. and Murray, N.E. EcoKl with an amino acid substitution in any one of seven DEAD-box motifs has impaired ATPase and endonuclease activities.//Nucleic Asids Res. 1998. 26,4828-4836.

75. Djordjevic, G.M. and Klaenhammer, T.R. Positive selection, cloning vectors for Gram positive bacteria based on a restriction endonuclease cassete.// Plasmid. 1996, 35, 281-295.

76. Doerfler, W. DNA Methylation: Molecular Biology and Biological Significance.// eds. Jost, J.P. and Saluz, H.P. Birkhauster Yerlag, Basel, 1993. 469-486.

77. Dorner, L.F. and Schildkraut, I. Direct selection of binding proficient/catalytic deficient variants of ВатШ endonuclease.//Nucleic Acids Res. 1994. 22, 1068-1074.

78. Dreier, J., Mac Williams, M.P. and Bickle, T. DNA cleavage by the type 1С restriction-modification enzyme £coR124I.// J.Mol.Biol. 1996. 264, 722-733.

79. Dryden, D.T.F., Cooper, L.P., Thorpe, P.H. and Byron, O. The in vitro asembly of the EcoYA type I DNA restriction/modification enzyme and its in vivo implication.// Biochemistry. 1997. 36,1065-1076.

80. Dussoix D. and Arber W. Host specificity of DNA produced by Escherichia coli: II. Control over acceptance of DNA from infecting phage X. II J. Mol. Biol. 1962. 5, 37-49.

81. Efimova, E.P., Delver, .P. and Belogurov, A.A. Alleviation of type I restriction in adenine methylase (dam) mutants of Escherichia coli.ll Mol.Gen.Genet. 1988. 214, 313-316.

82. Ellis, D.J., Dryden, D.T.F., Berge, Т., Edwardson, J.M. and Henderson, R.M. Direct observation of DNA translocation and cleavage by atomic forse microscopy.// Nature Struct.Biol. 1999. 6,15-17.

83. Embleton, M. L., Williams, S. A., Watson, M. A. and Halford, S. E. Specificity from the synapsis of DNA elements by the Sfil endonuclease.// J. Mol. Biol. 1999. 289:785-797.

84. Engler, P., Weng, A., Storb, U. Influence of CpG methylation and target spacing on V(D)J recombination in a transgenic substrat.// Mol.Cell.Biol. 1993.13,571-577.

85. Estrem, S.T., Gaal, Т., Ross, W. and Gourse, R.L. Identification of an UP element consensus sequence for bacterial promoters.//Proc Natl Acad Sci USA. 1998. 18, 9761-6.

86. Fedoroff, N.V. About maize transposable elements and development.// Cell. 1989. 56, 181-191.

87. Ferman, K., Creasey, W.A., Watson, G., Price, C. and Glover, S. W. Genetic and physical studies of restriction-deficient mutants of the Inc FIV plasmids R124 and R124/3.// Mol.Gen. Genet. 1983. 191, 145-153.

88. Fiandt, M., Hraedecna, Z., Lozeron, H.A.and Szybalski, W. The Bacteriophage Lambda. // Cold Spring Harbor Lab. New York. 1971.

89. Firman, K. and Szczelkun, M.D. Measuring motion on DNA by the type I restriction endonuclease £coR124I using triplex displasment.// The EMBO Journal. 2000. 19, 2094-2102.

90. Fuller-Pace, F.V., Cowan, G.M. and Murray, N.E. EcoA and EcoE alternatives to the EcoK family of type I restriction and modification systems of Escherichia coli.ll J.Mol.Biol. 1985. 186, 65-75.

91. Gabbara, S., and Bhagwat, A. S. Interaction of ЕсоШ1 endonuclease with DNA substrates containing single recognition sites // J. Biol. Chem. 1992. 267, 18623-18630.

92. Gardiner-Garden, M. and Frommer, M. CpG islands in vertebrate genomes. J.Mol.Biol. 1987.196, 261-268.

93. Gimble, F.S., Thorner, J. Homing of a DNA endonuclease gene by meiotic gene conversion in Saccharomyces cerevisae. //Nature. 1992. 357, 301-306.

94. Gimble, F.S.and Stephens, B.W. Substitutions in conserved dodecapeptide motifs that uncouple the DNA binding and DNA cleavage activities of Fl-Scel endonuclease. // J. Biol. Chem. 1995. 270, 5849-5856.

95. Glatman, L.I., Moroz, A.F., Yablokova, M.B., Rebentish, B.A., Kcholmina, G.V. A novel plasmid-mediated DNA restriction-modification system in E. coli. //Plasmid. 1980. 4, 350-351.

96. Glover, S., Schell, J., Symonds, N., Stacey, K. The control of the host induced modification by phage PI. // Genet. Res. 1963.18,1063-1067.

97. Glover, S.W. Genetics of the R-M systems in Haemophilus. II Heredity. 1978. 41, 123.

98. Goodrich-Blair, H. and Shub D.A. Beyond homing: competition between intron endonucleases confers a selective advantage on flanking genetic markers. // Cell. 1996. 84,. 211221.

99. Goedecke, К., Pignot, M., Goody,R.S., Scheidig, A.J. and Weinhold, E. Structure of the N6-adenin methyltransferase M.Tagl in complex with DNA and a cofactor analog.// Nature Struct. 2001.8,121-125.

100. Gong, W., О'Gar a, M., Blumenthal, R.M. and Cneng, X. Structure of Pvu II DNA-(cytosine N4) methyltransferase, an example of domain permutation and protein fold assignment.// Nucleic Acids Res. 1997. 25, 2702-2715.

101. Gorbalenya A.E. and Koonin E.V. Endonuclease (R) subunits of type-I and type-Ill restriction-modification enzymes contain a helicase-like domain. // FEBS Lett. 1991. 291, 277281.

102. Gottesman, S. and Maurizi, M.R. Regulation by proteolysis: energy-dependent proteases and their targets.//Microbiol.Rev. 1992. 56, 592-621.

103. Gowher, H., Leismann, O. and Jeltsch, A. DNA of Drosophila melanogaster contains 5-methylcytosine.// The EMBO Journal. 2000. 19, 6918-6923.

104. Greene, P.G., Gupta, M., Boyer, H.W., Brown, W.E. and Rosenberg, J.M. 1981. Sequence analysis of the DNA encoding the EcoRl endonuclease and methylase.// J.Biol. Chem. 256, 2141-2152

105. Grosskopf R., Wolf W., Kessler C. Two new restriction endonucleases Drall and Dralll from Deinococcus radiophilus.//Nucleic Acids Res. 1985. 13, 1517-1528.

106. Gunthert, U., Trautner, T.A. DNA methyltransferases of Bacillus subtilis and its bacteriophage.//Curr.Topics Microbiol.Immunol. 1984.108,11-22.

107. Hanahan D. Studies on transformation of Escherichia coli with plasmids. // J. Mol. Biol. 1983.166,557-580.

108. Hare, J.T. and Taylor, J.H. One role for DNA methylation in vertebrate cells is strand discrimination in mismatch repair.//Proc.Natl.Acad.Sci.USA. 1985. 82, 7350-7354.

109. Hashimoto-Gotoh, Т., Franklin, F.C., Nordheim, A. and Timmis, K.N. Specific-purpose plasmid cloning vector, I. Low copy number, temperature-sensitive, mobilization-defective, pSCl01-derived containment vectors.//Gene 1981. 16:227-235.

110. Hattman, S., Brooks, J.E., Masurekar, M. Sequence specificity of the PI modification methylase (m Eco PI) and the DNA methylase (M Eco dam) controlled by the Echerichia coli dam gene.// J.Mol.Biol. 1978.126,367.

111. Hattman, S. DNA methyltransferase-dependent transcription of the phage Mu mom gene.//Proc.Natl.Acad.Sci.USA. 1982. 79, 5518-5521.

112. Hattman, S. and Ives., J. SI nuclease mapping of the phage Mu mom gene promoter: a model for the regulation of mom expression.// Gene. 1984.29, 185-198.

113. Hedgpeth J., Goodman H.M., Boyer H.W. DNA nucleotide sequence restricted by the RI endonuclease. // Proc. Natl. Acad. Sci. USA. 1972. 9, 3448-3452.

114. Hedges, R.W. and Datta, N. J. R124, an fi R factor of a new compatibility class.// J Gen Microbiol. 1972. 71, 403-5.

115. Heidmann, S., Seifert, W., Kessler, C. and Domdey, H. Cloning, characterization and heterologous expression of the Smal restriction-modification system.// Nucleic Asids Res. 1989. 17, 9783-9796.

116. Herman, J.G. Hypermethylation of tumor suppressor genes in cancer.// Sem.Cancer Biol. 1999. 9,359-367.

117. Hinkle N.F., Miller R.V. pMG-7 mediated restriction of Pseudomonas aeruginosa phage DNAs is determined by a class II restriction endonuclease. // Plasmid. 1979.2, 387-393.

118. Holliday, R. The inheritance of epigenetic defects.// Science. 1987. 238, 163-170.

119. Holliday, R. Mutations and epimutations in mammalian cells.// Mutat.Res. 1991. 250, 351-363.

120. Huisman., T.T. and de Graaf, F.K. Negative control offae (K88) expression by the 'global' regulator Lrp is modulated by the 'local' regulator FaeA and affected by DNA methylation // Mol.Microbiol. 1995. 16, 943-953.

121. Jacobs, D. And Brown, N.L. Isolation and characterization of the M.Eael modification methylase.// Biochem. J. 1986. 238, 613-616.

122. Janscak, P., Abadjieva, A. and Firman, K. The type I restriction endonuclease R.£coR124I: over-production and biochemical properties.// J.Mol. Biol. 1996. 257, 977-991.

123. Janscak P, Dryden DT, Firman K. Analysis of the subunit assembly of the typeIC restriction-modification enzyme EcoRX241.// Nucleic Acids Res. 1998. 26,4439-45.

124. Janscak, P., Mac Williams, M. P., Sandmeier, U., Nagaraja, V. and Bickle, T.A. DNA translocation blockage, a general mechanism of cleavage site selection by type I restriction enzymes.//EMBO J. 1999. 18, 2638-2647.

125. Janscak, P., Sandmeier, U. and Bickle, T.A. Single amino acid substitutions in the HsdR subunit of the type IB restriction enzyme Ecokl uncouple the DNA translocation and DNA cleavage activities of the enzyme.//Nucleic Acids Res. 1999. 27,2638-2643.

126. Janscak, P., Sandeier, U., Szczelkun, M.D. and Bickle, T.A. Subunit assembly and mode of the DNA type III restriction endonucleasa EcoFll and £coP15L// Mol.Microbiol. 2001 12, 306-318.

127. Janulaitis, A.A., Klimaskauskas, S., Petrusyte, M., Butkus, V. Cytosine modification in DNA by Bcnl methylase yields N4-methylcytosine.// FEBS Lett. 1983. 161,131-134.

128. Janulaitis, A., Petrusyte, M., Maneliene, Z., Klimasauskas, S., Butkus, V. Purification and properties of the Eco51l restriction endonuclease and methylase-prototypes of a new class (type IV). //Nucleic Acids Res. 1992. 20, 6043-6049.

129. Johansen, S., Embley, T.M., Willasen, N.P. A family of nuclear homing endonucleases. // Nucleic Acids Res. 1993. 21.4405.

130. Kauc, L. and Piekarowicz, A. Purification and properties of a new restriction endonuclease from Heamophilus influenzae Rf.// Eur.J.Biochem. 1978. 92,417-426.

131. Keen, N.T., Tamaki, S., Kobayashi, D. and Trollinger, D. Improved broad-host-range plasmids for DNA cloning in gram-negative bacteria.// Gene 1988. 70, 191-197.

132. Kelly T.J., Smith H.O. A restriction enzyme from Hemophilus influenzae. II. Base sequence of the recognition site. // J. Mol. Biol. 1970. V. 51. P. 393-409.

133. Kessler, C.and Manta, V. Specificity of restriction endonucleases and DNA modification methyltransferases a review (Edition 3). // Gene. 1990. 92,1-248.

134. Kieny, M.P., Lathe, R. and Lecocq, J.-P. New versatile cloning and sequencing vectors based о bacteriophage M13.// Gene 1983. 26, 91-99.

135. Kim, Y.C., Grable, J.C., Love, R., Green, P.J. and Rosenberg, J.M. Refinement of ЕсоШ endonuclease structure: a revised protein chain tracing.// Science. 1990. 249,1307-1309.

136. Kiss, A.G., Posfai, C.C., Keller, C.C., Venetianer, P., Roberts, R.J. Nucleotide sequence of the BsuШ restriction-modification system. //Nucleic Acids Res. 1985. 13, 6403-6420.

137. Kiss, A., Posfai, G. Zsrka, G., Rasko, T. and Venetianer, P. Role of DNA minor groove interactions in substrate recognition by the M.Sinl and M.£coRII DNA (cytosine-5) methyltransferases.//Nucleic Acids Res. 2001.29, 3188-3194.

138. Klimaskauskas, S., Kumar, S., Roberts, R.J. and Cheng, X. Hhal methyltransferase flips its target base out of the DNA helix.// Cell. 1994.76, 357-369.

139. Kneale, G.G. A symmetrical model for the domain structure of type I DNA methyltransferases.// J.Mol. Biol. 1994.243, 1-5.

140. Kobayashi, I., Nobusato, A., Kobayashi-takahashi, N. and Uchiyama, I. Shaping the genome restriction-modification systems as mobile genetic elements. // Current Opinion in Genetics and Development. 1999. 9, 649-656.

141. Kong, H., Morgan, R.D., Maunus, R.E., Schildkraut, I. A unique restriction endonuclease, Bcgl, from Bacillus coagulans. //Nucleic Acids Res. 1993. 21, 987-991.

142. Kong, H., Roemer, S.E., Waite-Rees, P.A., Benner, J.S., Wilson, G.G. and Nwankwo, D.O. Characterization of Bcgl, a new kind of restriction-modification system.// J. Biol. Chem. 1994. 269, 683-690.

143. Kong, H., and Smith, C. L. Does Bcgl, a unique restriction endonuclease, require two recognition sites for cleavage?.// Biol. Chem. 1998. 379, 605-609.

144. Koons, M.D., Blumenthal, R.M. Characterization of pPvul, the autonomous plasmid from Proteus vulgaris that carries the genes of the PvuII restriction-modification system.// Gene. 1995. 19; 157, 73-9.

145. Korch, C., Hagblom, P., Normark, S. Sequence-specific DNA modification in Neisseria gonorrhoeae. И J. Bacteriol. 1983.155. 1324-1332.

146. Korch, C., Hagblom, P., Normark, S. Type III 5-methylcytosine modification of DNA in Neisseria gonorrhoeae. //J. Bacteriol. 1985. 161. 1236-1237.

147. Kosykh, V.G., Buryanov, Ya.I., Bayev, A.A. Molecular cloning of ЕсоШ1 endonuclease and methylase. // Mol. Gen. Genet. 1980. 178,717-718.

148. Kucherer, C., bother, H., Rolling, R., Schanzu, M.A. and Messer, W. Regulation of transcription of the chromosomal dnaA gene of Escherichia coli./l Mol.Gen.Genet. 1986. 205, 115-121.

149. Madsen, A. and Josephsen, J. Cloning and characterization of the Lactococcal plasmid-encoded type II restriction/modification system, I/aDII.// Applied & Environmental Microbiology. 1998. 64,2424-2431

150. Madsen, A. and Josephsen, J. Characterization of LlaCl, a new restriction-modification system from Lactococcus lactis subsp. cremoris W15.// J Biol Chem. 1998. 379, 443-449.

151. Makovets, S., Doronina, V.A. and Murray, N.E. Regulation of endonuclease activity by proteolysis prevents breakage of unmodified bacterial chromosomes by type I restriction enzymes.// Proc.Natl.Acad.Sci.USA. 1999. 96, 9757-9762.

152. Malone, Т., Blumenthal, R.M. and Cheng, X. Structure-guided analysis reveals nine sequence motifs conserved among DNA amino-methyl-transferases, and suggests a catalytic mechanism for these enzymes. // J.Mol.Biol. 1995. 253, 618-632.

153. Mandel M.and Higa, A.J. Calcium-dependent bacteriophage DNA infection. // J. Mol. Biol. 1970. 53, 159-162.

154. Maniatis, Т., Fritsch, E.F., Sambrook, J. Molecular cloning. A laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY. 1982.

155. Marinus, M.G. and Morris, N.R. Isolation of deoxyribonucleic asid methylase mutants of Escherichia coli K-12.// J.Bacteriol. 1973. 114,1143.

156. Marinus, M.G. DNA methylation influences trpR promoter activity in Escherichia coli K-12.// Mol.Gen.Genet. 1985. 200,185-186.

157. Marinus, M.G. DNA methylation in Echerichia coli.ll Ann.Rev.Genet. 1987. 21, 113-131.

158. Marinus, M.G. Methylation of DNA. In: Esherichia coli and Salmonella typhimurium: Cellular and Molecular Biology.// eds. Neidhardt, F.C., Ingraham, J.L.,Low, K.B., Magasanic, В., Schaechter, M. and Umbarger, H.E. Washington, DC. 1996. 782-791.

159. Martin, A.M., Horton, N.S., Lusetti, S., Reich, N.O. and Perona, J.J. Divalent metal dependence of site-specific DNA binding by EcoKV endonuclease // Biochemistry. 1999. 38, 8430-8439.

160. May, M.S. and Hattman, S. Analysis of bacteriophage deoxyribonucleic acid sequences methylated by host and R-factor-controlled enzymes.// J.Bacteriol. 1975.123, 768.

161. Matsuo, K., Silke, J., Georgiev, O., Marti, P., Giovannini, N. and Rungger, D. An embryonic demethylation mechanism involving binding of transcription factors to replicating DNA.// EMBO J. 1998. 17, 1446-1453.

162. Maxam, A.M. and Gilbert, W. A new method for sequencing DNA.// Proc. Nath. Acad. Sci. U! 1977. 74, 560-564.

163. McClelland, M. and Nelson, M. The 5' -GGATCC- 3' cleavage specificity of ВатШ is increase to 5' -CCGGATCCGG- 3' by sequential double methylation with M.Hpall and M. ВатШЛ Gene. 1988. 74,169-176

164. McClelland, M. and Nelson, M. Effect of site-specific methylation on DNA modification methyltransferases and restriction endonucleases.//Nucleic Acids Res. 1992. 20, 2145-2157.

165. McClelland, M., Nelson, M., Raschke, E. Effect of site-specific modification on restriction endonucleases and DNA modification methyltransferases. Nucleic Acids Res. 1994. 22, 3640-3659.

166. Mclnerney, E.M, Tsai, M.J, O'Malley, B.W, Katzenellenbogen, B.S. Analysis of estrogen receptor transcriptional enhancement by a nuclear hormone receptor coactivator.// Proc.Natl.Acad.Sci.USA. 1996. 93,10069-10073.

167. Meehan, R.R., Lewis, J.D., McKay, S., Kleiner, E.L. and Bird, A.P. Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs.// Cell. 1989. 58, 499-507.

168. Meehan, R.R., Lewis, J.D.and Bird, A.P. Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA.// Nucl.Acids Res. 1992. 20, 5085-5092.

169. Meisel A., Bickle T.A., Kruger D.H., Schroeder C. Type III restriction enzymes need two inversely oriented recognition sites for DNA cleavage. //Nature. 1992. 355, 467-469.

170. Meisel, A., Mackeldanz, P., Bickle, T. A., Kruger, D. H. and Schroeder, C. Type III restriction endonucleases translocate DNA in a reaction driven by recognition site-specific ATP hydrolysis.//EMBO J. 1995. 14:2958-2966.

171. Mise,K., and Nakajima,K. Purification of a new restriction endonuclease, Styl, from Escherichia coli carrying the hsct miniplasmid.// Gene. 1985. 30, 79-85.

172. Meselson M., Yuan R., Heywood J. Restriction and modification of DNA. // Annu. Rev. Biochem.1968. 41,. 447-466.

173. Miyahara,M. and Mise,K. Isolation and characterization of the StyDAl restriction endonuclease, a neoschizomer of ScrFI, from Escherichia coli K-12 carrying a small multicopy Hsdplasmid of Salmonella typhi origin.// Gene. 1993. 15, 83-86.

174. Monk, M. Epigenetic programming of differential gene expression in development and evolution.//Dev Genet. 1995. 17,188-197.

175. Murray, N.E. Type I restriction systems: sophisticated molecular machines (a legacy of Bertani and Weigle). Review.// Microbiol. Mol. Biol. Rev. 2000. 64,412-34.

176. Murchie, A.I.H. and Lilley, D.M.J. Base methilation and local DNA helix stability. Effect on the kinetics of cruciform extrusion.// J. Mol. Biol. 1989. 2205, 593-602.

177. Nagaraja V., Shepherd J.C.W., Pripfl Т., Bickle T.A. Two type I restriction enzymes from Salmonella species. II J. Mol. Biol. 1985. 182, 579-587.

178. Nelson, M., Raschke, E. and McClelland, M. Effect of site-specific methylation on restriction endonucleases and DNA modification methyltransferases.//Nucleic Acids Res. 1993. 21,3139-3154.

179. Newman, M., Strzelecka, Т., Dorner, L.F., Schildkraut, I. and Aggrwal, A.K. Structure of restriction endonuclease ВатШ and its relation to ЕсоШЛ Nature. 1994. 368, 660-664.

180. Newman, M., Lunnen, К., Wilson, G., Greci, J., Schildkraut, I., Phillips, S.E.V. Crystal structure of restriction endonuclease Bgll bound to its interrupted DNA recognition sequence.//. EMBO Journal. 1998.17, 5466-5476.

181. Nikolskaya I.I., Lopatina N.G., AnikeichevaN.V., Debov S.S. Determination of the recognition sites of cytosine DNA-methylases from Escherichia coli SK. // Nucleic Acids Res. 1979. 7,517-528.

182. Ng, H.-H. and Bird, A. DNA methylation and chromatin modification.// Curr.Opin.Gen.Dev. 1999. 9, 158-163.

183. Nou, X., Braaten, В., Kaltenbach,L. and Low, D. Differential binding of Lrp to two sets of pap DNA binding sites mediated by Pap I regulates Pap phase variation in Escherichia coli.// EMBO J. 1995. 14, 5785-5797.

184. Noyer-Weidner, M. and Trautner, T.A. Methylation of DNA in Procariotes. In DNA methylation: Molecular Biology and Biological Significance.// eds. Jost, J.P. and Saluz, H.P. Birkhauser, Basel, Switzerland. 1993.

185. O'Connor, C.D. and Humhreys, G.O. Expression of the ЕсоШ restriction-modification system and the construction of the positive-selection cloning vector.// Gene. 1982. 20, 219-229.

186. Oiler, A.R., Broek, W.V., Conrad M., Topal, M.D. Ability of DNA and spermidine to affect the activity of restriction endonucleases from several bacterial species. // Biochemistry. 1991. 30, 2543-2549.

187. Oka, A., Sigimoto, K., Takanami, M. and Hirota, Y. Replication origin of the Echerichia coli K-12 chromosome: the size and structure of the minimum DNA segment carrying the information for autonomous replication.// Mol.Gen.Genet. 1980. 178, 9-20.

188. Okano, M., Xie, S., and Li, E. Dnmt2 is not required for de novo and maintenance methylation of viral DNA in embryonic stem cells.//Nucl. Acids Res. 1998. 26, 2536-2540.

189. Okano, M., Bell, D.W., Haber, D.A. and Li, E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.// Cell. 1999. 99, 247-257.

190. O'Sullivan, D.J., Zagula, K. and Klaenhammer, T.R. In vivo restriction by Llal is encoded by three genes, arranged in an operon with llalM, on the conjugative Lactococcus plasmid pTR2030.// J.Bacteriol. 1995. 177,134-143.

191. O'Sullivan, D.J. and Klaenhammer, T.R. Control of exspression of Llal restriction in Lactococcus lactis./l Mol.Microbiol. 1998. 27,1009-1020.

192. Patnaik, P.K., Merlin, S., Polisky, B. Effect of altering GATC seguences in the plasmid ColEl primer promoter.// J.Bacteriology. 1990. 172, 1762-1762.

193. Peden, K.W. Revised sequence of the tetracycline-resistance gene of pBR322. // Gene. 1983. 22,277-280.

194. Pearson WR, Lipman DJ Improved tools for biological sequences comparison.// Proc Natl Acad Sci USA. 1988. 85: 2444-2448.

195. Pein, C-D., Reuter, M., Meisel, A., Cech, D. and Kruger, D. H. Activation of restriction endonuclease £coRII does not depend on the cleavage of stimulator DNA // Nucleic Acids Res. 1991. 19,5139-5142.

196. Perez-Rueda, E., Gralla, J.D and Collado-Vides, J. Genomic position analyses and the transcription machinery.// J. Mol. Biol. 1998.275, 165-170.

197. Perrin A., Buckle M., Dujon B. Asymmetrical recognition and activity of the l-Scel endonuclease on its site and on intron-exon junctions. // EMBO J. 1993. 12,2939-2947.

198. Pertzev A.V, Ruban N.M., Zakharova M.V., Beletzkaja I.V., Petrov S.I., Kravetz A.N., Solonin A.S. £co29kI, a novel plasmid encoded restriction endonuclease from Escherichia coli. II Nucl. Acids Res. 1992. 20,1991.

199. Peterson, K.R., Wertman, K.F., Mount, D.W., Marinus, M.G. Viability of Escherichia coli K-12 DNA adenine methylase (dam) mutants requires increased expression of specific genes in the SOS regulon.//Mol.Gen.Genet. 1985. 201,14-19.

200. Petrusyte M., Bitinaite J., Menkevicius S., Klimasauskas S., Butkus V., Janulaitis A. Restriction endonucleases of a new type. // Gene. 1988. 74, 89-91.

201. Piekarowicz A., Bickle T.A., Shepherd J.C.W., Ineichen K. The DNA sequence recognised by the Hinfill restriction endonuclease. // J. Mol. Biol. 1981. 146,167-172.

202. Piekarowicz, A. Preferential cleavage by restriction endonuclease Hinfill. И Acta Biochim. 1984.31,453-464.

203. Pingoud, A., and Jeltsch, A. Recognition and cleavage of DNA by type-II restriction endonucleases.//Eur. J. Biochem. 1997. 246, 1-22.

204. Plasterk, R.H.A., Vrieling, H. and Van de Putte, P. Transcription initiation of Mu mom depends on methylation of promoter region and a phage-coded transactivator.// Nature. 1983. 301,344-347.

205. Plasterk, R. H, Vollering, M., Brinkman, A., Van de Putte, P. Analyseof the methylation-regulalated Mu mom transcript.// Cell. 1984. 36,189-196.

206. Posfai, G. and Szybalski, W. A simple method for locating methylated bases in DNA, as applied to detect assymetric methylation by M.Fokl.// Gene. 1988. 69,147-151.

207. Posfai J, Bhagwat AS, Posfai G, Roberts RJ. Predictive motifs derived from cytosine methyltransferases.// Nucleic Acids Res. 1989. 17, 2421-35.

208. Powell, L.M. Dryden, D.T. and Murray, N.E. Sequence-specific DNA binding by EcoKl, a type IA DNA restriction enzyme.// J.Mol.Biol. 1998. 283, 963-976.

209. Prakash-Cheng, A.,Chung, S.S. and Ryu, J.-I. The expression and regulation of hsdK genes after conjugative transfer.// Mol.Gen.Genet. 1993. 241,491-496.

210. Predki, P.F., Nayak, L.M., Gottlieb, M.B.C. and Regan, L. Dissecting RNA-protein interaction: RNA -RNA recognition by Rop.// Cell. 1995. 80,41-50.

211. Price, C., Bickle, T.A., Firman, K. and Glover, S.W. Unequal crossig over a mechanism to generate changes in DNA sequence recognition by the type I restriction and modification enzymes.//J. Mol. Biol. 1989. 205,115-125.

212. Price, C., Lingner, J., Bickle, T.A., Firman, K. and Glover, S.W. Basis for changes in DNA recognition by the £coR124 and EcoR. 124/3 type I DNA restriction and modification enzymes.//J.Mol.Biol. 1989. 205,115-125.

213. Qiang, B.-Q. and Schildkraut, I. A type II restriction endonuclease with an eight nucleotide specificity from Streptomyces fimbriatus.il Nucleic Acids Res. 1984.12,4507-4516.

214. Qiang, B.-Q. and Schildkraut, I. Notl and Sfil: restriction endonucleases with octanucleotide recognition sequences.//Meth. Enzymol. 1987. 155,15-21.

215. Radman, M. and Wagner,R. Mismatch repair in Echerichia coli.il Ann.Rev.Genet. 1986. 20, 523-538.

216. Rak, B. and Von-Reutern, M. Insertion element IS5 contains a third gene.// EMBO J. 1984. 3, 807-811.

217. Raleigh, E.A.,Wilson, G. Escherichia coli K-12 restricts DNA containing 5-methylcytosine.// Proc.Natl.Acad.Sci.USA. 1986. 83, 9070-9074.

218. Raleigh, E. A. Organization and function of the mcrBC genes in Escherichia coli.ll Mol.Microbiol. 1992.169, 3243-3250

219. Razin, A. and Cedar, H. DNA methylation and genomic imprinting.// Cell. 1994. 77,473476.

220. Redaschi, N and Bickle, T.A. Posttranscriptional of EcoPI and EcoP15I restriction activity.//J.Mol.Biol. 1996. 257, 790-803.

221. Reddy, Y.V. and Rao, D.N. Binding of Eco?l5l DNA methyltransferase to DNA reveals a large structural distortion within the recognition sequence.// J Mol Biol. 2000. 298, 597-610.

222. Reinisch, K.M., Chen, L., Verdin, G.L. and Lipscomb, W.N. The crystal structure of Haelll methyltransferase covalently complexed to DNA: an extrahelical cytosine and rearranged base pairing.//Cell. 1995. 82,143-153.

223. Reuter, M., D. Kupper, A. Meisel, C. Schroeder, and D. H. Krueger. Cooperative binding properties of restriction endonuclease ЕсоШ\ with DNA recognition sites.// J. Biol. Chem. 1998. 273:8294 -8300.

224. Rimseliene, R., Vaisvila, R. and Janulaitis, A. The Eco 72IC gene specifies a trans-acting factor with influences expression of both DNA methyltransferase and endonuclease from the Eco721 restriction-modification system.// Gene. 1995. 157,217-219.

225. Rodicio, M.R. and Chater, K.F. Cloning and expression of the Sail restriction-modification system of the Streptomyces albus G.ll Mol. Gen. Genet. 1988. 213, 346-353.

226. Roberts, D., Hoopers, B.C., McClure, W. and Kleckner, N. IS 10 transposition is regulated by DNA adenine methylation.// Cell. 1985. 43,117-130.

227. Roberts, R.J. and Halford, S.E. Type II restriction endonuclease. // In Nuclease (eds. Linn, S.M., Lloyd, R.S. and Roberts, R.J.), Gold Spring Harbor Laboratory Press, Gold Spring Harbor, New-York. 1993. 35-88.

228. Roberts, R.J. and Macelis, D. REBASE-restriction enzymes and methylases.// Nucleic Acids Res. 1996. 25, 248-262.

229. Roberts, R. and Macelis, D. REBASE restriction enzymes and methylases.// Nucleic Acids Res. 1998. 1,338-50.

230. Roberts, R.J., Macelis, D., REBASE restriction enzymes and methylases.// Nucleic Acids Res. 1999.27,312-313.

231. Ross, W., Thompson, J.F., Newlands, J.T. and Gourse, R. L. E.coli Fis protein activates ribosomal RNA transcription in vitro and in vivo.// EMBO J. 1993. 9, 3733-3742.

232. Sain, B. and Murray, N.E. The hsd (host specificity) genes of E.coli K-12.// Mol.Gen.Genet. 1980, 20, 35-46.

233. Sanger, F., Nicklen, S., Coulson, A.R. DNA sequencing with chain-terminating inhibitors.// Proc. Natl. Acad. Sci. USA. 1977. 74, 5463-5467.

234. Sambrook, J., Fritsch, E.F., Maniatis, T. Molecular cloning: A laboratory manual, second ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. 1989.

235. Scavetta, R.D., Thomas, C.B., Walsh, M.A., Szegedi, S., Joachimiak, A., Gumport, R.I. and Churchill, M.E.A. Structure of Rsrl methyltransferase, a member of the N6-adenin P class of DNA methyltransferases.//Nucleic Acids Res. 2000. 28, 3950-3961.

236. Schauzu, M.A., Kucherer, C., Kolling ,R., Messer, W. And Lother,H. Transcripts within the replication origin, oriC of Escherichia coli.ll Nucleic Acids Res. 1987. 15, 2479-2497.

237. Schmid, K., Thomm, M., Laminet, A., Laue, F., Kessler, C., Stetter, K.O., Schmitt, R. Three new restriction endonucleases Mael, Maell and Maelll from Methanococcus aeolicus. II Nucl. Acids Res. 1984. 12,2619-2628.

238. Sears, L.E., Zhou, В., Alliota, J.M., Morgan, R.D. and Kong, H. BaeI, another unusual ifcgl-like restriction endonuclease //Nucleic Acids Res. 1995. 24, 3590-3592.

239. Seiler, A, Blocer, H., Frank, R. and Kahmann, R. The mom gene of bacteriophage Mu: the mechnism of methylation-dependent expression.// EMBO J. 1986. 5, 2719-2728.

240. Selent, U. A site-directed mutagenesis study to identify amino acids residues invovlved in the catalytic function of the restriction endonuclease EcoRV.// Biochemistry. 1992. 31, 48084815.

241. Selker, E.U., Fritz, D.Y. and Singer, M.J. Dense nonsymmetrical DNA methylation resulting from repeat-induced point mutation in Neurospora.il Science. 1993. 262, 1724-1728.

242. Selker, E.U., Gene silencing: repeats that count.// Cell. 1999. 97,157-160.

243. Seyfert, V.L., McMahon, S.B., Glenn, W.D., Yellen, A.J.,S., Uchatme,V.P., Cao, X.M. and Monroe, J.G. Methylation of an immediate-early inducible gene as a mechanism for В cell tolerance induction.// Science. 1990. 250, 797-800.

244. Shinomiya, T. and Sato, S. A site specific endonuclease from Thermus thermophilus 111, Tth\ 1II. // Nucleic Acids Res. 1980. 8,43-56.

245. Siksnys, V., Zareckaya, N., Vaisvila, R., Timinskas, A., Stakenas, P., Butkus, V. and Janulaitis, A. CAATTG-specific restriction-modification muni genes from Mycoplasma: sequence similarties between R.Munl and EcoRl.ll Gene. 1994.142,1-8.

246. Siksnys, V., Skirgaila, R., Sasnauskas, G., Urbanke, C., Cherny, D., Grazulis,S., and Huber, R. J. The CfrlOI restriction enzyme is functional as a tetramer// Mol. Biol. 1999. 291, 1105-1118.

247. Sharma, M., Ellis R.L., Hinton, D.M. Identification of a family of bacteriophage T4 genes encoding proteins similar to those present in group I introns of fungi and phages. // Proc. Natl. Acad. Sci. USA. 1992. 89. 6658-6662.

248. Shub, D.A., Coerzee, Т., Hall, D.H., Belfort, M. The self-splicing introns of bacteriophage T4. In: Karam J.D. (Eds.) Molecular biology of bacteriophage T4. // ASM Press. Washington. DC. 1994. 186-192.

249. Shub, D.A, Goodrich-Blair, H., Eddy, S.R. Amino acid sequence motif of group I intron endonucleases is conserved in open reading frames of group II introns. // Trends Biochem. Sci. 1994. 19. 402-404.

250. Scavetta, R.D., Thomas, C.B., Walsh, M.A., Szegedi, S., Joachimiak, A., Gumport, R.I., Churchill, M.E. Structure of RsrI methyltransferase, a member of the N6-adenine beta class of DNA methyltransferases.// Nucleic Acids Res. 2000. 28, 3950-61.

251. Skrzypek, E. and Piekarowicz, A. The EcoDXXl restriction and modification system: cloning the genes and homology to type I restriction and modification systems.// Plasmid. 1989. 21, 195-204.

252. Smith, H.O., Wilcox, K.W. A restriction enzyme from Hemophilus influenzae. I. Purification and general properties. //J. Mol. Biol. 1970. 51, 379-391.

253. Smith, D.W., Garland,A.M., Herman,G.,Enns,R.E., Baker,T.A. and Zyskind,J. Importance of state of methylation of oriC GATC sites in initiation of DNA replication in Echerichia coli.// EMBO J. 1985. 4, 319-13327.

254. Sohail, A., Ives, C.L. and Brooks, J.E. Purification and characterization of С.ВатШ, a regulator of the ВатШ restriction-modification system.// Gene. 1995. 157, 227-228.

255. Som, S. and Friedman, S. Autogenous regulation of the EcoRII methylase gene at the trancriptional level: effect of 5-azacytidine.// EMBO J. 1993.12, 4297-4303

256. Som, S. and Freidman, S. Regulation of EcoRII methyltransferase: effect of mutations on gene expression and in vivo binding to the promoter regoin.// Nucleic Acids Res. 1994. 24, 53475353.

257. Som, S. and Freidman, S. Characterization of the intergenic region which regulates the Mspl restriction-modification system.// J.Bacteriology. 1997.179, 964-967.

258. Sozhamannan, S. and Stitt, B.L. Effect on mRNA degradation by Escherichia coli transcription termination factor Rho and pBR322 copy number control protein Rop.// J.Mol.Biol. 1997. 268,689-703.

259. Spencer, .E., Enster, G., Burcin, M.M., Allis, C.D., Zhou, J., Mizzen, C.A., McKenna, N.J., Onate, S.A., Tsai, S.Y., Tsai, M.J. and O'Malley, B.W. Steroid receptor coactivator-1 is a histone acetyltransferase.//Nature. 1997. 389,1 94-198.

260. Sternberg, N. and Hoess, R. Molecular genetics of bacteriphage PI.// Annu.Rev.Genet. 1983.17,123-154.

261. Sternberg, N. Evidence that adenine methylation influences DNA-protein interactions in Echerichia coli.// J.Bacteriology. 1985. 164, 490-493.

262. Studier, F. W. and Bandyopadhyay, P.K. Model for how type I restriction enzymes select cleavage sites in DNA.// Proc. Natl Acad. Sci. USA. 1988. 85,4677-4681.

263. Sved, J. and Bird, A. The expectedeguilibrium of the CpG dinucleotidein vertebrate genomes under a mutation model.//Proc.Natl.Acad.Sci.USA. 1990. 87, 4692-4696.

264. Suri, B. and Bickle, T.A. EcoA: the first member of a new family of type I restriction modification systems gene organization and enzymatic activities.// J.Mol.Biol., 1985, 186, 7785.

265. Sullivan, K.M., Macdonald H.J. and Saunders. Characterization of DNA restriction and modification activities in Neisseria species. IIFEMS Microbiol. Lett. 1987. 44, 389-393.

266. Sullivan, K.M. and Saunders, J.R. Nucleotide sequence and genetic organization of the JVgoPII restriction-modification system of Neisseria gonorrhoeae. И Mol. Gen. Genet. 1989. 216, 380-387.

267. Sutcliffe, J.G. Nucleotide sequence of the ampicillin resistance gene of Escherichia coli plasmid pBR322. // Proc. Natl. Acad. Sci. USA. 1978. 75, 3737-3741.

268. Sutherland, E. McrBC a multisubunit GTP-dependent restriction endonuclease.// J.Mol.Biol. 1992. 225, 327-348.

269. Swisshelm, K., Disteche, C.M. and Thorvaldsen, J. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon.// Mutat.Res. 1990. 237, 131-146.

270. Szczelkun, M.D., Dillingham, M.S., Janscak, P., Firman, K. and Halford, S.E. Repercussions of DNA tracking by the type 1С restriction endonuclease EcoR12Al on linear, circular and catenated substrates.// EMBO J. 1996. 15, 6335-6347.

271. Szczelkun, M.D., Janscak, P., Firman, K. and Halford,S.E. Selection of non-specific DNA cleavage sites by the type 1С restriction endonuclease .EcoRI241.// J. Mol. Biol. 1997. 271,112— 123.

272. Тао, Т., Walter, J., Brennan, K.J., Cotterman, M.M. and Blumenthal, R.M. Seguence, internal homology and high-level exspression of the gene for a DNA-(cytosine N4)-methyltransferase, U.Pvull./I Nucleic Acids Res. 1989. 17, 4161-4174.

273. Тао, Т.,Bourne, J.C. and Blumenthal, R.M. A family of regulatory genes associated with type II restriction-modification systems.// J.Bacteriology. 1991. 173,367-1375.

274. Тао, T. and Bluemental, R.M. Sequence and characterization of pvuIIR, the Pvull endonuclease, and ofpvuIIC, its regulatory gene.//J.Bacteriol. 1992. 174,3395-3398.

275. Tasheva, E.S and Roufa, D.J. Densely methylated DNA islands in mammalian chromosomal replication origins.//Mol.Cell.Biol. 1994. 14, 5636-5644.

276. Tazi, J. and Bird, A. Alternative chromatin structure at CpG islands.// Cell. 1990. 60, 909920.

277. Terry, B.J., Jack, W.E., and Modrich, P. Facilitated diffusion during catalysis by ЕсоШ endonuclease. Nonspecific interactions in ЕсоШ catalysis // J. Biol. Chem. 1985. 260,1313013137.

278. Terry, B. J., Jack, W. E., and Modrich, P. Mechanism of specific site location and DNA cleavage by EcoR I endonuclease // Gene Amplif. Anal. 1987. 5,103-118.

279. Thompson, J.D., Gibson, T.J., Plewniak, F., Jeanmougin, F., Higgins, D.G. The CLUSTALX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools.// Nucleic Acids Res. 1997. 15: 4876-4882.

280. Thorns, B. and Wackernagel, W. Genetic control of damage-inducible restriction alleviation in Escherichia coli K12: an SOS function not repressed by lexA.// Mol.Gen.Genet. 1984. 197,297-303.

281. Timinskas, A., Butkus, V. and Janulaitis, A. Sequence motifs characteristic for DNA cytosine-N4. and DNA [adenine-N6] methyltransferases. Classification of all DNA methyltransferases. // Gene. 1995. 157, 3-11.

282. Titheradge, A.J.B., Tement, D. and Murray, N.E. A third family of allelic hsd genes in Salmonella enterica: sequence comparisons with related proteins identify conserved regions implicated in restriction of DNA.// Mol. Microbiol. 1996. 22, 437-447.

283. Tollefsbol, Т.О. and Hutchson, С.A. Control of methylation spreading in synthetic DNA seguences by the murine DNA methyltransferase.// J.Mol.Biol. 1997. 269, 494-504.

284. Tomb, J.F., White, O., Kerlavage, A.R., Clayton, R.A., Sutton, G.G., Fleichmann, R.D., Ketchum, K.A., Klenk, H.P., Gill, S., Dougherty, B.A. The complete genome sequence of the gastric pathogen Helicobacter pylori. //Nature. 1997. 388, 539-547.

285. Topal, M. D., Thresher, R. J., Conrad, M. and Griffith, J. NaeI endonuclease binding to pBR322 DNA induces looping.// Biochemistry. 1991. 30,2006 -2010.

286. Toth, M., Lichtenberg, U. and Doerfler, W. Genomic sequencing reveals a 5-methylcytosine-free domain in active promoters and the spreading of preimposed methylation patterns.//Proc.Natl.Acad.Sci.USA. 1989. 86,3728-3732.

287. Toyota, M. and Issa, J.-P.J. CpG island methylator phenotypes in aging and cancer.// Sem.Cancer Biol. 1999. 9, 349-357.

288. Turker, M.S., Mummaneni, P. and Bishop,P.L. Region- and cell type-specific de novo DNA methylation in cultured mammalian cells.//Somat.Cell Mol.Genet. 1991. 17, 151-157.

289. Turker, M.S. The establishment and maintenance of DNA methylation patterns in mouse somatic cells.// Sem.Cancer Biol. 1999. 9, 329-337.

290. Vertino, P.M., Yen, R.W., Gao, J. and Baylin, S.B. De novo methylation of CpGislandsequences in human fibroblasts overexpressing DNA (cytosine-5)-methyltransferase.// Mol.Cell.Biol. 1996. 16,4555-4565.

291. Vijesurier, R.M., Carlock, L., Blumenthal, R.M.and Dunbar, J.C. Role and mechanism of action of С Pvull, a regulatory protein conserved among restriction-modification systems.// J.Bacteriology. 2000. 182, 477-487.

292. Vitkute, J., Maneliene, Z., Petrusyte, M. and Janulaitis, А.// Врй, a new 5cgl-like restriction endonuclease, which recognizes a symmetric sequence.//Nucleic Acids Res. 1997. 25, 4444-4446.

293. Vitor, J.M.B. and Morgan, R.D. Two novel restriction endonucleases from Campylobacter jejuni // Gene. 1995. 157,109-110.

294. Weiserova, M., Dutta, C.F. and Firman, K. A novel mutant of the type I restriction-modification enzyme EcoRllAl is alterated at a key stage of the subunit assembly pathway.// J. Mol. Biol. 2000. 304,301-310.

295. Willcock, D.F., Dryden, D.T.F. and Murray, N.E. A mutation analysis of the two motifs common to adenine methyltransferases.// EMBO J. 1994. 13, 3902-3908.

296. Wilson G.G. Organization ofrestriction-modificationsystems. //Nucleic Acids Res. 1991. 19,2539-2565.

297. Wilson, G.G. and Murray, N.E. Restriction and modification systems.// Annu. Rev. Genet. 1991.25,585-627.

298. Wilson G.G. Amino acid sequence arrangements of DNA-methyltransferases. // Methods Enzymology. 1992. 216,259-279.

299. Winkler, F.K. The crystal structure of EcoRV endonuclease and of its complexes with cognate and non-cognate DNA fragments.// EMBO J. 1993. 12,1781-1795.

300. Wintjens, R. and Rooman, M. Structural classification of HTH DNA-binding domains and protein-DNA-interaction models.// J.Mol.Biology. 1996. 262,294-313.

301. Wright, D.J., Jack, W.E. and Modrich, P. The kinetic mechanism of EcoRI endonuclease //J.Biol. Chem. 1999. 274, 31896-31902.

302. Wood, W.B. Host specificity of DNA produced by Escherichia coli: Bacterial mutations affecting the restriction and modification of DNA.// J. Mol. Biol. 1966. 16, 118-133.

303. Xia, Y., Burbank D.E., Van Etten ,J.L. Restriction endonuclease activity induced by NC-1A virus infection of a Chlorella-like green alga. // Nucleic Acids Res. 1986. 14, 6017-6030.

304. Yang, С. C., and Topal, M. D. Nonidentical DNA-binding sites of endonuclease NaeI recognize different families of sequences flanking the recognition site // Biochemistry. 1992. 31, 9657-9664.

305. Yanisch-Perron, C.,Vieira, J. and Messing, J. Improving M13 phage cloning vectors and host strains: nucleotide sequence of the M13mpl8 and pUC vectors.// Gene. 1985. 33, 103-119.

306. Yoshimori, R.N. A genetic and biochemical analysis of the restriction and modification of DNA by resistance transfer factors. // Ph.D. Thesis. University of California. San Francisco. 1971.

307. Yuan, R. The reaction mechanism of type I restriction endonucleases. In: Chirikjian J.G. (Eds.) Gene Amplification and Analysis. Part I. Restriction endonucleases. // Elsevier/North. Holland Biomedical Press. New York. 1981. 45-72.

308. Yuan, R. Structure and mechanism of multifunctional restriction endonucleases. // Annu. Rev. Biochem. 1981. 50,285-319.

309. Zakharova, M.V., Kravetz, A.N., Beletskaya, I.V., Repyk, A.V., Solonin, A.S. Cloning and sequences of the genes encoding the QrBI restriction-modification system from Citrobacter freundii.ll Gene. 1993. 129. 77-81.

310. Zebala, J.F., Choi, J., Trainor, J. and Barany, F.Characterization of steady state, single turnover and binding kinetics of the Tagl restriction endonuclease.// J.Biol.Chem. 1992. 267, 8106-8116.