Роль систем репарации и структуры хроматина эукариотической клетки в интеграции ретровирусов
Диссертация
Отобранных по экспрессии трансдуцированного в составе ретровируса гена устойчивости к 0418. В то время как в полученных 14 клонах МНЕ1(-) клеток, содержащих единичные провирусы в различных положениях ДНК, наблюдали, как и в КНЕ1(+) клетках, стандартные 6-нуклеотидные повторы, для пяти провирусов в МНЕ1(-) клетках обнаружили 5-нуклеотидные повторы. Эти данные могут свидетельствовать о вовлечении… Читать ещё >
Содержание
- СПИСОК СОКРАЩЕНИЙ
- ВВЕДЕНИЕ
- 2. ОБЗОР ЛИТЕРАТУРЫ
- 2. 1. Повреждение эукариотической ДНК при интеграции ретровирусов
- 2. 2. Механизмы репарации двунитевых разрывов ДНК в клетках эукариот
- 2. 3. Семейство Р13К-подобных киназ
- 2. 4. Формирование клеточного ответа на повреждения ДНК
- 2. 5. Клеточные белки и интеграция ретровирусов
- 2. 6. Хроматин и интеграция ретровирусов
- 3. МАТЕРИАЛЫ И МЕТОДЫ
- 4. РЕЗУЛЬТАТЫ И ОБСУЖДЕНИЕ
- 4. 1. Анализ нуклеотидной последовательности участков между ДНК провируса и клетки-хозяина в NHEJ (+) и NHEJ (-) клетках
- 4. 2. Рапарация промежуточного комплекса интеграции в реакции in vitro
- 4. 3. Влияние ингибиторов семейства Р13К-киназ на процесс репарации in vitro
- 4. 4. Влияние структуры хроматина на интеграцию ретровирусной ДНК in vitro
- 5. ВЫВОДЫ
Список литературы
- Aiyar, А., Р. Hindmarsh, А. М. Skalka, and J. Leis. 1996. Concerted integration of linearretroviral DNA by the avian sarcoma virus integrase in vitro: dependence on both long terminal repeat termini. J Virol 70:3571−80.
- Ajimura, M. , S. H. Leem, and H. Ogawa. 1993. Identification of new genes required formeiotic recombination in Saccharomyces cerevisiae. Genetics 133:51−66.
- Anderson, C. W., and S. P. Lees-Miller. 1992. The nuclear serine/threonine protein kinaseDNA-PK. Crit Rev Eukaryot Gene Expr 2:283−314.
- Bai, Y. , and L. S. Symington. 1996. A Rad52 homolog is required for RAD51-independentmitotic recombination in Saccharomyces cerevisiae. Genes Dev 10:2025−37.
- Bannister, A, J., T. M. Gottlieb, T. Kouzarides, and S. P. Jackson. 1993. c-Jun isphosphorylated by the DNA-dependent protein kinase in vitro- definition of the minimal kinase recognition motif. Nucleic Acids Res 21:1289−95.
- Baumann, P., and S. C. West. 1998. DNA end-joining catalyzed by human cell-free extracts. Proc Natl Acad Sci U S A 95:14 066−70.
- Baumann, P., and S. C. West. 1998. Role of the human RAD51 protein in homologousrecombination and double- stranded-break repair. Trends Biochem Sci 23:247−51.
- Bertuch, A., and V. Lundblad. 1998. Telomeres and double-strand breaks: trying to makeends meet. Trends Cell Biol 8:339−42.
- Blasina, A., I. V. de Weyer, M. C. Laus, W. H. Luyten, A. E. Parker, and C. H. McGowan.1999. A human homologue of the checkpoint kinase Cdsl directly inhibits Cdc25 phosphatase. Curr Biol 9:1−10.
- Bosma, G. C, R, P. Custer, and M. J. Bosma. 1983. A severe combined immunodeficiencymutation in the mouse. Nature 301:527−30.
- Brin, E., J. Y i, A. M. Skalka, and J. Leis. 2000. Modeling the late steps in HIV-1 retroviralintegrase-catalyzed DNA integration. J Biol Chem 275:39 287−95.
- Brown, E. J., and D. Baltimore. 2000. ATR disruption leads to chromosomal fragmentationand early embryonic lethality. Genes Dev 14:397−402.
- Brown, P. O., B. Bowerman, H. E. Varmus, and J. M. Bishop. 1989. Retroviral integration: structure of the initial covalent product and its precursor, and a role for the viral IN protein. Proc Natl Acad Sci U S A 86:2525−9.
- Brunborg, G., and D. H. Williamson. 1978. The relevance of the nuclear division cycle toradiosensitivity in yeast. Mol Gen Genet 162:277−86.
- Burma, S., B. P. Chen, M. Murphy, A. Kurimasa, and D. J. Chen. 2001. A T MPhosphorylates Histone H2AX in Response to DNA Double-strand Breaks. J Biol Chem 276:424 627.
- Busse, P. M. , S. K. Bose, R. W. Jones, and L. J. Tolmach. 1978. The action of caffeine on Xirradiated HeLa cells. III. Enhancement of X-ray-induced killing during G2 arrest. Radiat Res 76:292−307.
- Carty, M. P., M. Zernik-Kobak, S. McGrath, and K. Dixon. 1994. U V Hght-induced DNAsynthesis arrest in HeLa cells is associated with changes in phosphorylation of human singlestranded DNA-binding protein. Embo J 13:2114−23.
- Chow, S. A., K. A. Vincent, V. Elhson, and P. O. Brown. 1992. Reversal of integration andDNA splicing mediated by integrase of human immunodeficiency virus. Science 255:723−6.
- Cirillo, L. A., F. R. Lin, I. Cuesta, D. Friedman, M. Jamik, and K. S. Zaret. 2002. Opening ofCompacted Chromatin by Early Developmental Transcription Factors HNF3 (FoxA) and GATA-4. Mol Cell 9:279−89.
- Clarke, A. R., C. A. Purdie, D. J. Harrison, R. G. Morris, C. C. Bird, M. L. Hooper, and A.H. Wyllie. 1993. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 362:849−52.
- Coffin J.M., S. H. H., H.E. Varmus. 1997. Retroviruses. Cold Spring Harbor LaboratoryPress.
- Cortez, D., Y. Wang, J. Qin, and S. J. Elledge. 1999. Requirement of ATM-dependentphosphorylation of brcal in the DNA damage response to double-strand breaks. Science 286:1162−6.
- Craigie, R. 1995. Resolving a resolvase. Nat Struct Biol 2:607−9.
- Craigie, R., T. Fujiwara, and F. Bushman. 1990. The IN protein of Moloney murine leukemiavirus processes the viral DNA ends and accomplishes their integration in vitro. Cell 62:829−37.
- Craigie, R., and K. Mizuuchi. 1985. Mechanism of transposition of bacteriophage Mu: structure of a transposition intermediate. Cell 41:867−76.
- Critchlow, S. E., and S. P. Jackson. 1998. D N A end-joining: from yeast to man. TrendsBiochem Sci 23:394−8.
- Daniel, R., R. A. Katz, G. Merkel, J. C. Hittle, T. J. Yen, and A. M. Skalka. 2001. Wortmannin potentiates integrase-mediated killing of lymphocytes and reduces the efficiency of stable transduction by retroviruses. Mol Cell Biol 21:1164−72.
- Daniel, R., R. A. Katz, and A. M. Skalka. 1999. A role for DNA-PK in retroviral DNAintegration. Science 284:644−7.
- Daniel, R., S. Litwin, R. A. Katz, and A. M. Skalka. 2001. Computational analysis ofretrovirus-induced scid cell death. J Virol 75:3121−8.
- Dhar, R., W. L. McClements, L. W. Enquist, and G. F. Vande Woude. 1980. Nucleotidesequences of integrated Moloney sarcoma provirus long terminal repeats and their host and viral junctions. Proc Natl Acad Sci U S A 77:3937−41.
- Dorshkind, K., G. M. Keller, R. A. Phillips, R. G. Miller, G. C. Bosma, M. O’Toole, and M .J. Bosma. 1984. Functional status of cells from lymphoid and myeloid tissues in mice with severe combined immunodeficiency disease. J Immunol 132:1804−8.
- Downs, J. A., N. F. Lowndes, and S. P. Jackson. 2000. A role for Saccharomyces cerevisiaehistone H2A in DNA repair. Nature 408:1001−4.
- Durocher, D., and S. P. Jackson. 2001. DNA-PK, A T M and ATR as sensors of DNAdamage: variations on a theme? Curr Opin Cell Biol 13:225−31.
- EUedge, S. J. 1996. Cell cycle checkpoints: preventing an identity crisis. Science 274:166 472,
- Engelman, A., K. Mizuuchi, and R. Craigie. 1991. HIV-1 DNA integration: mechanism ofviral DNA cleavage and DNA strand transfer. Cell 67:1211−21.
- Essers, J., H. van Steeg, J. de Wit, S. M. Swagemakers, M. Vermeij, J. H. Hoeijmakers, andR. Kanaar. 2000. Homologous and non-homologous recombination differentially affect DNA damage repair in mice. Embo J 19:1703−10.
- Famet, C. M. , and W. A. Haseltine. 1991. Determination of viral proteins present in thehuman immunodeficiency virus type 1 preintegration complex. J Virol 65:1910−5.
- Famet, C. M. , and W. A. Haseltine. 1990. Integration of human immunodeficiency virus type
- DNA in vitro. Proc Natl Acad Sci U S A 87:4164−8.
- Fitzgerald, M. L., and D. P. Grandgenett. 1994. Retroviral integration: in vitro host siteselection by avian integrase. J Virol 68:4314−21.
- Flint S J, E. L., Krug RM, Racaniello VR, Skalka AM. 2000. Principles of virolog: molecular biology. Pathogenesis, and contorl. A S M Press, Washington D.C.
- Fujiwara, T., and R. Craigie. 1989, Integration of mini-retroviral DNA: a cell-free reactionfor biochemical analysis of retroviral integration. Proc Natl Acad Sci U S A 86:3065−9.
- Fujiwara, T., and K. Mizuuchi. 1988. Retroviral DNA integration: structure of an integrationintermediate. Cell 54:497−504.
- Gaillard, P. H., E. M. Martini, P. D. Kaufman, B. Stillman, E. Moustacchi, and G. Almouzni.1996. Chromatin assembly coupled to DNA repair: a new role for chromatin assembly factor I. Cell 86:887−96.
- Gallay, P., S. Swingler, J. Song, F. Bushman, and D. Trono. 1995. HIV nuclear import isgoverned by the phosphotyrosine-mediated binding of matrix to the core domain of integrase. Cell 83:569−76.
- Game, J. C. 2000. The Saccharomyces repair genes at the end of the century. Mutat Res451:277−93.
- Gately, D. P., J. C. Hittle, G. K. Chan, and T. J. Yen. 1998. Characterization of A T Mexpression, localization, and associated DNA-dependent protein kinase activity. Mol Biol Cell 9:2361−74.
- Gerton, J. L., D. Herschlag, and P. O. Brown. 1999. Stereospecificity of reactions catalyzedby HIV-1 integrase. J Biol Chem 274:33 480−7.
- GottUeb, T. M., and S. P. Jackson. 1993. The DNA-dependent protein kinase: requirementfor DNA ends and association with Ku antigen. Cell 72:131−42.
- Grunstein, M. 1990. Nucleosomes: regulators of transcription. Trends Genet 6:395−400.
- Haber, J. E. 1999. DNA repair. Gatekeepers of recombination. Nature 398:665, 667.
- Haber, J. E. 1998. The many interfaces of Mrel 1. Cell 95:583−6.
- Hall, J. M. , M. K. Lee, B. Newman, J. E. Morrow, L. A. Anderson, B. Huey, and M. C. King.1990. Linkage of early-onset famiUal breast cancer to chromosome I7q21. Science 250:1684−9.
- Hall-Jackson, C. A., D. A. Cross, N. Mortice, and C. Smythe. 1999. ATR is a caffeinesensitive, DNA-activated protein kinase with a substrate specificity distinct from DNA-PK. Oncogene 18:6707−13.
- Hammarsten, O., and G. Chu. 1998. DNA-dependent protein kinase: DNA binding andactivation in the absence of Ku. Proc Natl Acad Sci U S A 95:525−30.
- Hanakahi, L. A., M. Bartlet-Jones, C. Chappell, D. Pappin, and S. C. West. 2000. Binding ofinositol phosphate to DNA-PK and stimulation of double- strand break repair. Cell 102:721−9.
- Hansen, M. S., and F. D. Bushman. 1997. Human immunodeficiency virus type 2preintegration complexes: activities in vitro and response to inhibitors. J Virol 71:3351−6.
- Hartwell, L. H., and T. A. Weinert. 1989. Checkpoints: controls that ensure the order of cellcycle events. Science 246:629−34.
- Hartzog, G. A., and F. Winston. 1997. Nucleosomes and transcription: recent lessons fromgenetics. Curr Opin Genet Dev 7:192−8.
- Herrmann, G., T. Lindahl, and P. Schar. 1998. Saccharomyces cerevisiae L IF l: a functioninvolved in DNA double-strand break repair related to mammalian XRCC4. Embo J 17:4188−98.
- Hindmarsh, P., M. Johnson, R. Reeves, and J. Leis. 2001. Base-pair substitutions in aviansarcoma virus U5 and U3 long terminal repeat sequences alter the process of DNA integration in vitro. J yirol 75:1132−41.
- Hirao, A., Y. Y. Kong, S. Matsuoka, A. Wakeham, J. Ruland, H. Yoshida, D. Liu, S. J. Elledge, and T. W. Mak. 2000. DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 287:1824−7.
- Ho, K. S., and R. K. Mortimer. 1973. Induction of dominant lethality by x-rays inradiosensitive strain of yeast. Mutat Res 20:45−51.
- Horton, R., S. R. Mumm, and D. P. Grandgenett. 1991. Phosphorylation of the avianretrovirus integration protein and proteolytic processing of its carboxyl terminus. J Virol 65:1141−8.
- Hughes, S. H., A. Mutschler, J. M. Bishop, and H. E. Varmus. 1981. A Rous sarcoma virusprovirus is flanked by short direct repeats of a cellular DNA sequence present in only one copy prior to integration. Proc Natl Acad Sci U S A 78:4299−303.
- Iftode, C, Y. Daniely, and J. A. Borowiec. 1999. RepHcation protein A (RPA): theeukaryotic SSB. Crit Rev Biochem Mol Biol 34:141−80.
- Ivanov, E. L., V. G. Korolev, and F. Fabre. 1992. XRS2, a DNA repair gene ofSaccharomyces cerevisiae, is needed for meiotic recombination. Genetics 132:651−64.
- Ivanov, E. L., N. Sugawara, J. Fishman-Lobell, and J. E. Haber. 1996. Genetic requirementsfor the single-strand annealing pathway of double- strand break repair in Saccharomyces cerevisiae. Genetics 142:693−704.
- Jeggo, P. A., A. M. Carr, and A. R. Lehmann. 1998. Splitting the A T M: distinct repair andcheckpoint defects in ataxia- telangiectasia. Trends Genet 14:312−6.
- Jeggo, P. A., A. M. Carr, and A. R. Lehmann. 1998. Splitting the A T M: distinct repair andcheckpoint defects in ataxia-telangiectasia. Trends Genet 14:312−6.
- Jenuwein, T., and C. D. Allis. 2001. Translating the histone code. Science 293:1074−80.
- Jordan, A., P. Defechereux, and E. Verdin. 2001. The site of HIV-1 integration in the humangenome determines basal transcriptional activity and response to Tat transactivation. Embo J 20:1726−38.
- Kalpana, G. V., S. Marmon, W. Wang, G. R. Crabtree, and S. P. Goff. 1994. Binding andstimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5. Science 266:2002−6.
- Kanaar, R., J. H. Hoeijmakers, and D. C. van Gent. 1998. Molecular mechanisms of DNAdouble strand break repair. Trends Cell Biol 8:483−9.
- Katz, R. A., G. Merkel, J. Kulkosky, J. Leis, and A. M. Skalka. 1990. The avian retroviral INprotein is both necessary and sufficient for integrative recombination in vitro. Cell 63:87−95.
- Katz, R. A., and A. M. Skalka. 1994. The retroviral enzymes. Annu Rev Biochem 63:133−73.
- Kim, S. T., D. S. Lim, C. E. Canman, and M. B. Kastan. 1999. Substrate specificities andidentification of putative substrates of A T M kinase family members. J Biol Chem 274:37 538−43.
- Kim, U. J., M. Han, P. Kayne, and M. Gmnstein. 1988. Effects of histone H4 depletion onthe cell cycle and transcription of Saccharomyces cerevisiae. Embo J 7:2211−9.
- Kwon, H., A. N. Imbalzano, P. A. Khavari, R. E. Kingston, and M. R. Green. 1994. Nucleosome dismption and enhancement of activator binding by a human SWl/SNF complex. Nature 370:477−81.
- Lakin, N. D., B. C. Hann, and S. P. Jackson. 1999. The ataxia-telangiectasia related proteinATR mediates DNA-dependent phosphorylation of p53. Oncogene 18:3989−95.
- Lamer, J. M., H. Lee, and J. L, Hamlin. 1994. Radiation effects on D N A synthesis in adefined chromosomal replicon. Mol Cell Biol 14:1901−8.
- Leclercq, I., F. Mortreux, M. Cavrois, A. Leroy, A. Gessain, S. Wain-Hobson, and E. Wattel.2000. Host sequences flanking the human T-cell leukemia virus type 1 provirus in vivo. J Virol 74:2305−12.
- Lee, M. S., and R. Craigie. 1998. A previously unidentified host protein protects retroviralDNA from autointegration. Proc Natl Acad Sci U S A 95:1528−33.
- Lee, M. S., and R. Craigie. 1994. Protection of retroviral DNA from autointegration: involvement of a cellular factor. Proc Natl Acad Sci U S A 91:9823−7.
- Lee, S. E., R. A. Mitchell, A. Cheng, and E. A. Hendrickson. 1997. Evidence for DNA-PKdependent and -independent DNA double-strand break repair pathways in mammalian cells as a function of the cell cycle. Mol Ceh Biol 17:1425−33.
- Lees-Miller, S. P., R. Godbout, D. W. Chan, M. Weinfeld, R. S. Day, 3rd, G. M. Barron, andJ. AUalunis-Tumer. 1995. Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell line. Science 267:1183−5.
- L i, L., C. M. Famet, W. F. Anderson, and F. D. Bushman. 1998. Modulation of activity ofMoloney murine leukemia virus preintegration complexes by host factors in vitro. J Virol 72:212 531.
- L i, L., J. M. Olvera, K. E. Yoder, R. S. Mitchell, S. L. Butler, M. Lieber, S. L. Martin, and F.D. Bushman. 2001. Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection. Embo J 20:3272−81.
- L i, Z., T. Otevrel, Y. Gao, H. L. Cheng, B. Seed, T. D. Stamato, G. E. Taccioli, and F. W.Ah. 1995. The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V (D)J recombination. Cell 83:1079−89.
- Liang, F., M. Han, P. J. Romanienko, and M. Jasin. 1998. Homology-directed repair is amajor double-strand break repair pathway in mammalian cells. Proc Natl Acad Sci U S A 95:5172−7.
- Lim, D. S., S. T. Kim, B. Xu, R. S. Maser, J. Lin, J. H. Petrini, and M. B. Kastan. 2000. A T M phosphorylates p95/nbsl in an S-phase checkpoint pathway. Nature 404:613−7.
- Liu, V. F., and D. T. Weaver. 1993. The ionizing radiation-induced replication protein Aphosphorylation response differs between ataxia telangiectasia and normal human cells. Mol Cell Biol 13:7222−31.
- Loidl, P. 1994. Histone acetylation: facts and questions. Chromosoma 103:441−9.
- Lorch, Y., J. W. LaPointe, and R. D. Komberg. 1987. Nucleosomes inhibit the initiation oftranscription but allow chain elongation with the displacement of histones. Cell 49:203−10.
- Lowe, S. W., E. M. Schmitt, S. W. Smith, B. A. Osborne, and T. Jacks. 1993. p53 is requiredfor radiation-induced apoptosis in mouse thymocytes. Nature 362:847−9.
- Luger, K., A. W. Mader, R. K. Richmond, D. F. Sargent, and T. J. Richmond. 1997. Crystalstructure of the nucleosome core particle at 2.8 A resolution. Nature 389:251−60.
- Majors, J. E., and H. E. Varmus. 1981. Nucleotide sequences at host-pro viral junctions formouse mammary tumour virus. Nature 289:253−8.
- Matsuoka, S., M. Huang, and S. J. Elledge. 1998. Linkage of A T M to cell cycle regulation bythe Chk2 protein kinase. Science 282:1893−7.
- McPherson, C. E., E. Y. Shim, D. S. Friedman, and K. S. Zaret. 1993. An active tissuespecific enhancer and bound transcription factors existing in a precisely positioned nucleosomal array. Cell 75:387−98.
- Megee, P. C, B. A. Morgan, and M. M. Smith. 1995. Histone H4 and the maintenance ofgenome integrity. Genes Dev 9:1716−27.
- Meiering, C. D., and M. L. Linial. 2001. Historical perspective of foamy virus epidemiologyand infection. Clin Microbiol Rev 14:165−76.
- Miller, M. D., C. M. Famet, and F. D. Bushman. 1997. Human immunodeficiency virus type1 preintegration complexes: studies of organization and composition. J Virol 71:5382−90.
- Mizuuchi, K. 1992. Polynucleotidyl transfer reactions in transpositional DNA recombination. J Biol Chem 267:21 273−6.
- Moreau, K., C. Tome-Celer, C. Faure, G. Verdier, and C. Ronfort. 2000. In vivo retroviralintegration: fidelity to size of the host DNA duplication might Be reduced when integration occurs near sequences homologous to LTR ends. Virology 278:133−6.
- Morgan, D. O. 1995. Principles of CDKregulation. Nature 374:131−4.
- Morgan, S. E., and M. B. Kastan. 1997. Dissociation of radiation-induced phosphorylation ofrephcation protein A from the S-phase checkpoint. Cancer Res 57:3386−9.
- MuUer, H. P., and H. E. Varmus. 1994. DNA bending creates favored sites for retroviralintegration: an explanation for preferred insertion sites in nucleosomes, Embo J 13:4704−14.
- Murray, A. W. 1992. Creative blocks: cell-cycle checkpoints and feedback controls. Nature359:599−604.
- Naito, T., A. Matsuura, and F. Ishikawa. 1998. Circular chromosome formation in a fissionyeast mutant defective in two A T M homologues. Nat Genet 20:203−6.
- Nurse, P. 1997. Checkpoint pathways come of age. Cell 91:865−7.
- Olive, P. L. 1998. The role of DNA single- and double-sti-and breaks in cell killing byionizing radiation. Radiat Res 150:842−51.
- Paillard, S., and F. Strauss. 1991. Analysis of the mechanism of interaction of simian Kuprotein with DNA. Nucleic Acids Res 19:5619−24.
- Painter, R. B., and B. R. Young. 1980. Radio sensitivity in ataxia-telangiectasia: a newexplanation. Proc Nati Acad Sei U S A 77:7315−7.
- Paques, P., and J. E. Haber. 1999. Multiple pathways of recombination induced by doublestrand breaks in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 63:349−404.
- PauU, T. T., and M. Gellert. 1998. The 3' to 5' exonuclease activity of Mre 11 facilitatesrepair of DNA double-strand breaks. Mol Cell 1:969−79.
- Paull, T. T., E. P. Rogakou, V. Yamazaki, C. U. Kirchgessner, M. Gellert, and W. M.Bonner. 2000. A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. CurrBiol 10:886−95.
- Pruss, D., P. D. Bushman, and A. P. Wolffe. 1994. Human immunodeficiency virus integrasedirects integration to sites of severe DNA distortion within the nucleosome core. Proc Natl Acad Sci USA91:5913−7.
- Pryciak, P. M. , A. Sil, and H. E. Varmus. 1992. Retroviral integration into minichromosomesin vitro. Embo J 11:291−303.
- Pryciak, P. M. , and H. E. Varmus. 1992. Nucleosomes, DNA-binding proteins, and DNAsequence modulate retroviral integration target site selection. Cell 69:769−80.
- Resnick, M. A., and P. Martin. 1976, The repair of double-strand breaks in the nuclear DNAof Saccharomyces cerevisiae and its genetic control. Mol Gen Genet 143:119−29.
- Rice, J. C, and C. D. AUis. 2001. Code of silence. Nature 414:258−61.
- Rice, P., R. Craigie, and D. R. Davies. 1996. Retroviral integrases and their cousins. CurrOpin Struct Biol 6:76−83.
- Roe, T., S. A. Chow, and P. O. Brown. 1997. 3'-end processing and kinetics of 5'-end joiningduring retroviral integration in vivo. J Virol 71:1334−40.
- Rogakou, E. P., C. Boon, C. Redon, and W. M. Bonner. 1999. Megabase chromatin domainsinvolved in DNA double-strand breaks in vivo. J Cell Biol 146:905−16.
- Rogakou, E. P., D. R. Pilch, A. H. Orr, V. S. Ivanova, and W. M. Bonner. 1998. D N Adouble-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273:5858−68.
- Rohdewohld, H., H. Weiher, W. Reik, R. Jaenisch, and M. Breindl. 1987. Retrovirusintegration and chromatin structure: Moloney miurine leukemia pro viral integration sites map near DNase I-hypersensitive sites. J Virol 61:336−43.
- Roth, D. B., and J. H. Wilson. 1985. Relative rates of homologous and nonhomologousrecombination in transfected DNA. Proc Natl Acad Sei U S A 82:3355−9.
- Sambrook J, F. E., Maniatis T. 1989. Molecular cloning. Cold Spring Harbor LaboratoryPress, Cold Spring Harbor, NY.
- Sarkaria, J. N. , R. S. Tibbetts, E. C. Busby, A. P. Kennedy, D. E. Hill, and R. T. Abraham.1998. Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. Cancer Res 58:4375−82.
- Schar, P., G. Herrmann, G. Daly, and T. Lindahl. 1997. A newly identified DNA ligase ofSaccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks. Genes Dev 11:1912−24.
- Scherdin, U. , K. Rhodes, and M. Breindl. 1990. Transcriptionally active genome regions arepreferred targets for retrovirus integration. J Virol 64:907−12.
- Schlegel, R., and A. B. Pardee. 1986. Caffeine-induced uncoupling of mitosis from thecompletion of DNA rephcation in mammalian cells. Science 232:1264−6.
- Shapiro, J. A. 1979. Molecular model for the transposition and replication of bacteriophageMu and other transposable elements. Proc Natl Acad Sei U S A 76:1933−7.
- Shiloh, Y. 2001. A T M and ATR: networking cellular responses to DNA damage. Curr OpinGenet Dev 11:71−7.
- Shim, E. Y., C. Woodcock, and K. S. Zaret. 1998. Nucleosome positioning by the wingedhelix transcription factor HNF3. Genes Dev 12:5−10.
- Shimotohno, K., S. Mizutani, and H. M. Temin. 1980. Sequence of retrovirus provirusresembles that of bacterial transposable elements. Nature 285:550−4.
- Shinohara, A., and T. Ogawa. 1995. Homologous recombination and the roles of doublestrand breaks. Trends Biochem Sci 20:387−91.
- Singleton, B. K., A. Priestley, H. Steingrimsdottir, D. Gell, T. Blunt, S. P. Jackson, A. R.1.hmann, and P. A. Jeggo. 1997. Molecular and biochemical characterization of xrs mutants defective in Ku80. Mol Cell Biol 17:1264−73.
- Smerdon, M. J., and A. Conconi. 1999. Modulation of DNA damage and DNA repair inchromatin. Prog Nucleic Acid Res Mol Biol 62:227−55.
- Smith, G. C, and S. P. Jackson. 1999. The DNA-dependent protein kinase. Genes Dev13:916−34.
- Strahl, B. D., and C. D. AUis. 2000. The language of covalent histone modifications. Nature403:41−5.
- Suzuki, K., S. Kodama, and M. Watanabe. 1999. Recruitment of A T M protein to doublestrand DNA irradiated with ionizing radiation. J Biol Chem 274:25 571−5.
- Tan, T. L., J. Essers, E. Citterio, S. M. Swagemakers, J. de Wit, F. E. Benson, J. H. Hoeijmakers, and R. Kanaar. 1999. Mouse Rad54 affects DNA conformation and DNA-damageinducedRad51 foci formation. CurrBiol 9:325−8.
- Teo, S. H., and S. P. Jackson. 1997. Identification of Saccharomyces cerevisiae DNA hgase1.: involvement in DNA double-strand break repair, Embo J 16:4788−95.
- Teo, S. H., and S. P. Jackson. 2000. Liflp targets the DNA ligase Lig4p to sites of DNAdouble-strand breaks. CurrBiol 10:165−8.
- Thacker, J. 1999. A surfeit of RAD51-like genes? Trends Genet 15:166−8.
- Thompson, L. H., and P. A. Jeggo. 1995. Nomenclature of human genes involved in ionizingradiation sensitivity. MutatRes 337:131−4.
- Tibbetts, R. S., D. Cortez, K. M. Brumbaugh, R. Scully, D. Livingston, S. J. Elledge, and R.T. Abraham. 2000. Functional interactions between B R C A l and the checkpoint kinase ATR during genotoxic stress. Genes Dev 14:2989−3002.
- Triglia, T., M. G. Peterson, and D. J. Kemp. 1988. A procedure for in vitro amplification ofDNA segments that lie outside the boundaries of known sequences. Nucleic Acids Res 16:8186.
- Verdin, E. 1991. DNase I-hypersensitive sites are associated with both long terminal repeatsand with the intragenic enhancer of integrated human immunodeficiency virus type 1. J Virol 65:6790−9.
- Verdin, E., P. Paras, Jr., and C. Van Lint. 1993. Chromatin disruption in the promoter ofhuman immimodeficiency virus type 1 during transcriptional activation. Embo J 12:3249−59.
- Verreault, A, , P. D. Kaufman, R. Kobayashi, and B. Stillman. 1996. Nucleosome assemblyby a complex of CAF-1 and acetylated histones H3/H4. Cell 87:95−104.
- Wang, H., J. Guan, A. R. Perrauh, Y. Wang, and G. Ihakis. 2001. Replication Protein A2Phosphorylation after DNA Damage by the Coordinated Action of Ataxia Telangiectasia-Mutated and DNA-dependent Protein Kinase. Cancer Res 61:8554−63.
- Ward, I. M. , and J. Chen. 2001. Histone H2AX Is Phosphorylated in an ATR-dependentManner in Response to Replicational Stress. J Biol Chem 276:47 759−47 762.
- West, R. B., M. Yaneva, and M. R. Lieber. 1998. Productive and nonproductive complexesof Ku and DNA-dependent protein kinase at DNA termini. Mol Cell Biol 18:5908−20.
- Wilson, T. E., U. Grawunder, and M. R. Lieber. 1997. Yeast DNA ligase IV mediates nonhomologous DNA end joining. Nature 388:495−8.
- Wold, M. S. 1997. Replication protein A: a heterotrimeric, single-stranded DNA-bindingprotein required for eukaryotic DNA metabolism. Annu Rev Biochem 66:61−92.
- Wolffe, A. 1998. Chromatin: structure and function. Academic press, London.
- Wood, R. D. 1996. DNA repair in eukaryotes. Annu Rev Biochem 65:135−67.
- Wooster, R., G. BigneU, J. Lancaster, S. Swift, S. Seal, J. Mangion, N. Collins, S. Gregory, C. Gumbs, and G. Micklem. 1995. Identification of the breast cancer susceptibility gene BRCA2. Nahire 378:789−92.
- Xu, Y., and D. Baltimore. 1996. Dual roles of A T M in the cellular response to radiation andin cell growth control. Genes Dev 10:2401−10.
- Yoder, K. E., and F. D. Bushman. 2000. Repair of gaps in retroviral D N A integrationintermediates. J Virol 74:11 191−200.
- Young, В. R., and R. B. Painter. 1989. Radioresistant DNA synthesis and human geneticdiseases. Hum Genet 82:113−7.
- Zhang, H., G. Tombline, and B. L. Weber. 1998. B R C A l, BRCA2, and DNA damageresponse: collision or collusion? Cell 92:433−6.
- Агол В.И. Разнообразие вирусов. 1997. Соросовский образовательный журнал.№ 4.С. 11−16.
- Зеленин А.В., Кайгородов В. А., Прасолов В.С.Генная терапия сегодня и завтра. 1998. Молекулярная биология. 32(2). 219−28
- Прасолов B.C., Иванов Д. С. Ретровирусные векторы в генной терапии. 2000. Вопросымедицинской химии. 46(3). 207−25
- Глазер В.М. Гомологичная генетическая рекомбинация. 1998. Соросовскийобразовательный журнал. № 7. 13−21.