vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biologyvestnik-bio-msu-269Research ArticleМолекулярная биологияMolecular biologyРЕПАРАЦИЯ ДНК В СОСТАВЕ ХРОМАТИНАREPAIR OF CHROMATINIZED DNAГерасимоваНадежда СергеевнаGerasimovaN. S.

мл. науч. сотр. кафедры биоинженерии

gerasimova@mail.bio.msu.ruПестовНиколай АлександровичPestovN. A.

канд. биол. наук, доц. кафедры биотехнологии, биоинженерии и биохимии биологического факультета

pestov79@gmail.comКулаеваОльга ИгоревнаKulaevaO. I.

канд. биол. наук, ст. науч. сотр. кафедры биоинженерии

olga.studitskaia@fccc.eduНикитинДмитрий ВалерьевичNikitinD. V.

канд. биол. наук, ст. науч. сотр. кафедры биоинженерии

dvnikit@yandex.ruКирпичниковМихаил ПетровичKirpichnikovM. P.

академик РАН, проф., докт. биол. наук, декан, зав. кафедрой биоинженерии

kirpichnikov@inbox.ruСтудитскийВасилий МихайловичStuditskyV. M.

докт. биол. наук, гл. науч. сотр. кафедры биоинженерии

vasily.studitsky@fccc.eduбиологический факультет МГУRussian FederationФГБОУ ВПО “Мордовский государственный университет им. Н.П. Огарёва”Russian Federationбиологический факультет МГУРоссияD.V. , M.P. Kirpichnikov, V.M. StuditskyRussian Federation201517082015032125Copyright © Герасимова Н.С., Пестов Н.А., Кулаева О.И., Никитин Д.В., Кирпичников М.П., Студитский В.М., 20152015Герасимова Н.С., Пестов Н.А., Кулаева О.И., Никитин Д.В., Кирпичников М.П., Студитский В.М.Gerasimova N.S., Pestov N.A., Kulaeva O.I., Nikitin D.V., Kirpichnikov M.P., Studitsky V.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/269

Ежедневно под действием внешних и внутренних факторов в клетке возникают десятки тысяч повреждений ДНК. Восстановление корректной структуры ДНК — репарация — важнейший процесс поддержания работоспособности генома. В ядрах эукариотических клеток ДНК упакована в хроматин, в котором должна успешно проходить ее репарация. Исторически сложилось представление, что гистоны временно удаляются с репарируемой ДНК. В то же время накапливается все больше сведений в пользу того, что структура хроматина влияет на репарационный ответ, ограничивая его распространение, изменяя активность ферментов репарации, участвуя в определении пути ответа и возобновлении функциональности восстановленного участка генома.

Endogenous and exogenous agents generate tens of thousands lesions in the DNA of every cell daily. Maintenance of the DNA integrity by repair systems is crucial for genome functioning. Eukaryotic nuclear DNA is tightly packaged into chromatin. DNA repair should be considered in these conditions. Recent studies lead to a revision of the historical “access — repair — restore” paradigm of the DNA damage response indicating the chromatin structure as an active player in the process regulating localization, pathway choice, enzyme activity and restoration of the repaired locus function.

хроматинрепарациянуклеосомагистонДНКразрывы ДНКокислительный стрессРНК-полимераза IIобзорchromatinrepairnucleosomehistoneDNADNA breaksoxidative stressRNA polymerase IIreviewРоссийский научный фондReferencesChristmann M., Tomicic M.T., Roos W.P., Kaina B. Mechanisms of human DNA repair: an update // Toxicology. 2003. Vol. 193. N 1—2. P. 3—34.Christmann M., Tomicic M.T., Roos W.P., Kaina B. Mechanisms of human DNA repair: an update // Toxicology. 2003. Vol. 193. N 1—2. P. 3—34.Dexheimer T.S. DNA repair pathways and mechanisms // DNA repair of cancer stem cells / Ed. by L.A. Mathews, S.M. Cabarcas and E.M. Hurt. Dordrecht: Springer Science + Business Media. 2013. P. 19—32.Dexheimer T.S. DNA repair pathways and mechanisms // DNA repair of cancer stem cells / Ed. by L.A. Mathews, S.M. Cabarcas and E.M. Hurt. Dordrecht: Springer Science + Business Media. 2013. P. 19—32.Luger K., Mader A.W., Richmond R.K., Sargent D.F., Richmond T.J. Crystal structure of the nucleosome core particle at 2.8 А resolution // Nature. 1997. Vol. 389. N 6648. P. 251—260.Luger K., Mader A.W., Richmond R.K., Sargent D.F., Richmond T.J. Crystal structure of the nucleosome core particle at 2.8 А resolution // Nature. 1997. Vol. 389. N 6648. P. 251—260.Arents G., Moudrianakis E.N. The histone fold: a ubiquitous architectural motif utilized in DNA compaction and protein dimerization // Proc. Natl. Acad. Sci. USA. 1995. Vol. 92. N 24. P. 11170—11174.Arents G., Moudrianakis E.N. The histone fold: a ubiquitous architectural motif utilized in DNA compaction and protein dimerization // Proc. Natl. Acad. Sci. USA. 1995. Vol. 92. N 24. P. 11170—11174.Noll M. Internal structure of the chromatin subunit // Nucleic Acids Res. 1974. Vol. 1. N 11. P. 1573—1578.Noll M. Internal structure of the chromatin subunit // Nucleic Acids Res. 1974. Vol. 1. N 11. P. 1573—1578.Wigler M.H., Axel R. Nucleosomes in metaphase chromosomes // Nucleic Acids Res. 1976. Vol. 3. N 6. P. 1463—1471.Wigler M.H., Axel R. Nucleosomes in metaphase chromosomes // Nucleic Acids Res. 1976. Vol. 3. N 6. P. 1463—1471.Hayes J.J., Tullius T.D., Wolffe A.P. The structure of DNA in a nucleosome // Proc. Natl. Acad. Sci. USA. 1990. Vol. 87. N 19. P. 7405—7409.Hayes J.J., Tullius T.D., Wolffe A.P. The structure of DNA in a nucleosome // Proc. Natl. Acad. Sci. USA. 1990. Vol. 87. N 19. P. 7405—7409.Strand J.M., Scheffler K., Bj ras M., Eide L. The distribution of DNA damage is defined by region-specific susceptibility to DNA damage formation rather than repair differences // DNA Repair (Amst.). 2014. Vol. 18. P. 44—51.Strand J.M., Scheffler K., Bj ras M., Eide L. The distribution of DNA damage is defined by region-specific susceptibility to DNA damage formation rather than repair differences // DNA Repair (Amst.). 2014. Vol. 18. P. 44—51.Tijsterman M., de Pril R., Tasseron-de Jong J.G., Brouwer J. RNA Polymerase II transcription suppresses nucleosomal modulation of UV-induced (6—4) photoproduct and cyclobutane pyrimidine dimer repair in yeast // Mol. Cell. Biol. 1999. Vol. 19. N 1. P. 934—940.Tijsterman M., de Pril R., Tasseron-de Jong J.G., Brouwer J. RNA Polymerase II transcription suppresses nucleosomal modulation of UV-induced (6—4) photoproduct and cyclobutane pyrimidine dimer repair in yeast // Mol. Cell. Biol. 1999. Vol. 19. N 1. P. 934—940.Odell I.D., Wallace S.S., Pederson D.S. Rules of engagement for base excision repair in chromatin // J. Cell. Physiol. 2013. Vol. 228. N 2. P. 258—266.Odell I.D., Wallace S.S., Pederson D.S. Rules of engagement for base excision repair in chromatin // J. Cell. Physiol. 2013. Vol. 228. N 2. P. 258—266.Nouspikel T., Hanawalt P.C. DNA repair in terminally differentiated cells // DNA repair (Amst.). 2002. Vol. 1. N 1. P. 59—75.Nouspikel T., Hanawalt P.C. DNA repair in terminally differentiated cells // DNA repair (Amst.). 2002. Vol. 1. N 1. P. 59—75.Blainey P.C., Luo G., Kou S.C., Mangel W.F., Verdine G.L., Bagchi B., Xie X.S. Nonspecifically bound proteins spin while diffusing along DNA // Nat. Struct. Mol. Biol. 2009. Vol. 16. N 12. P. 1224—1229.Blainey P.C., Luo G., Kou S.C., Mangel W.F., Verdine G.L., Bagchi B., Xie X.S. Nonspecifically bound proteins spin while diffusing along DNA // Nat. Struct. Mol. Biol. 2009. Vol. 16. N 12. P. 1224—1229.Odell I.D., Newick K., Heintz N.H., Wallace S.S., Pederson D.S. Non-specific DNA binding interferes with the efficient excision of oxidative lesions from chromatin by the human DNA glycosylase, NEIL1 // DNA repair (Amst.). 2010. Vol. 9. N 2. P. 134—143.Odell I.D., Newick K., Heintz N.H., Wallace S.S., Pederson D.S. Non-specific DNA binding interferes with the efficient excision of oxidative lesions from chromatin by the human DNA glycosylase, NEIL1 // DNA repair (Amst.). 2010. Vol. 9. N 2. P. 134—143.Odell I.D., Barbour J.E., Murphy D.L., Della-Maria J.A., Sweasy J.B., Tomkinson A.E., Wallace S.S., Pederson D.S. Nucleosome disruption by DNA ligase III-XRCC1 promotes efficient base excision repair // Mol. Cell. Biol. 2011. Vol. 31. N 22. P. 4623—4632.Odell I.D., Barbour J.E., Murphy D.L., Della-Maria J.A., Sweasy J.B., Tomkinson A.E., Wallace S.S., Pederson D.S. Nucleosome disruption by DNA ligase III-XRCC1 promotes efficient base excision repair // Mol. Cell. Biol. 2011. Vol. 31. N 22. P. 4623—4632.Hinz J.M., Rodriguez Y., Smerdon M.J. Rotational dynamics of DNA on the nucleosome surface markedly impact accessibility to a DNA repair enzyme // Proc. Natl. Acad. Sci. USA. 2010. Vol. 107. N 10. P. 4646—4651.Hinz J.M., Rodriguez Y., Smerdon M.J. Rotational dynamics of DNA on the nucleosome surface markedly impact accessibility to a DNA repair enzyme // Proc. Natl. Acad. Sci. USA. 2010. Vol. 107. N 10. P. 4646—4651.Murr R., Loizou J.I., Yang Y.G., Cuenin C., Li H., Wang Z.Q., Herceg Z. Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks // Nat. Cell Biol. 2006. Vol. 8. N 1. P. 91—99.Murr R., Loizou J.I., Yang Y.G., Cuenin C., Li H., Wang Z.Q., Herceg Z. Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks // Nat. Cell Biol. 2006. Vol. 8. N 1. P. 91—99.Smerdon M.J. DNA repair and the role of chromatin structure // Curr. Opin. Cell Biol. 1991. Vol. 3. N 3. P. 422—428.Smerdon M.J. DNA repair and the role of chromatin structure // Curr. Opin. Cell Biol. 1991. Vol. 3. N 3. P. 422—428.Gospodinov A., Herceg Z. Shaping chromatin for repair // Mutat. Res. 2013. Vol. 752. N 1. P. 45—60.Gospodinov A., Herceg Z. Shaping chromatin for repair // Mutat. Res. 2013. Vol. 752. N 1. P. 45—60.Mandemaker I.K., Vermeulen W., Marteijn J.A. Gearing up chromatin: A role for chromatin remodeling during the transcriptional restart upon DNA damage // Nucleus. 2014. Vol. 5. N 3. P. 203—210.Mandemaker I.K., Vermeulen W., Marteijn J.A. Gearing up chromatin: A role for chromatin remodeling during the transcriptional restart upon DNA damage // Nucleus. 2014. Vol. 5. N 3. P. 203—210.Bird A.W., Yu D.Y., Pray-Grant M.G., Qiu Q., Harmon K.E., Megee P.C., Grant P.A., Smith M.M., Christman M.F. Acetylation of histone H4 by Esa1 is required for DNA double-strand break repair // Nature. 2002. Vol. 419. N 6905. P. 411—415.Bird A.W., Yu D.Y., Pray-Grant M.G., Qiu Q., Harmon K.E., Megee P.C., Grant P.A., Smith M.M., Christman M.F. Acetylation of histone H4 by Esa1 is required for DNA double-strand break repair // Nature. 2002. Vol. 419. N 6905. P. 411—415.Downs J.A., Allard S., Jobin-Robitaille O., Javaheri A., Auger A., Bouchard N., Kron S.J., Jackson S.P., Cote J. Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites // Mol. Cell. 2004. Vol. 16. N 6. P. 979—990.Downs J.A., Allard S., Jobin-Robitaille O., Javaheri A., Auger A., Bouchard N., Kron S.J., Jackson S.P., Cote J. Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites // Mol. Cell. 2004. Vol. 16. N 6. P. 979—990.Fousteri M., Mullenders L.H. Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects // Cell Res. 2008. Vol. 18. N 1. P. 73—84.Fousteri M., Mullenders L.H. Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects // Cell Res. 2008. Vol. 18. N 1. P. 73—84.van Attikum H., Gasser S.M. The histone code at DNA breaks: a guide to repair? // Nat. Rev. Mol. Cell Biol. 2005. Vol. 6. N 10. P. 757—765.van Attikum H., Gasser S.M. The histone code at DNA breaks: a guide to repair? // Nat. Rev. Mol. Cell Biol. 2005. Vol. 6. N 10. P. 757—765.Soria G., Polo S.E., Almouzni G. Prime, repair, restore: the active role of chromatin in the DNA damage response // Mol. Cell. 2012. Vol. 47. N 4. P. 497—510.Soria G., Polo S.E., Almouzni G. Prime, repair, restore: the active role of chromatin in the DNA damage response // Mol. Cell. 2012. Vol. 47. N 4. P. 497—510.Downey M., Durocher D. Chromatin and DNA repair: the benefits of relaxation // Nat. Cell Biol. 2006. Vol. 8. N 1. P. 9—10.Downey M., Durocher D. Chromatin and DNA repair: the benefits of relaxation // Nat. Cell Biol. 2006. Vol. 8. N 1. P. 9—10.Khurana S., Kruhlak M.J., Kim J., Tran A.D., Liu J., Nyswaner K., Shi L., Jailwala P., Sung M.H., Hakim O., Oberdoerffer P. A macrohistone variant links dynamic chromatin compaction to BRCA1-dependent genome maintenance // Cell Rep. 2014. Vol. 8. N 4. P. 1049—1062.Khurana S., Kruhlak M.J., Kim J., Tran A.D., Liu J., Nyswaner K., Shi L., Jailwala P., Sung M.H., Hakim O., Oberdoerffer P. A macrohistone variant links dynamic chromatin compaction to BRCA1-dependent genome maintenance // Cell Rep. 2014. Vol. 8. N 4. P. 1049—1062.Li M.L., Yuan G., Greenberg R.A. Chromatin yo-yo: expansion and condensation during DNA repair // Trends Cell Biol. 2014. Vol. 24. N 11. P. 616—618.Li M.L., Yuan G., Greenberg R.A. Chromatin yo-yo: expansion and condensation during DNA repair // Trends Cell Biol. 2014. Vol. 24. N 11. P. 616—618.Keogh M.C., Kim J.A., Downey M. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery // Nature. 2006. Vol. 439. N 7075. P. 497—501.Keogh M.C., Kim J.A., Downey M. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery // Nature. 2006. Vol. 439. N 7075. P. 497—501.Kusch T., Florens L., Macdonald W.H., Swanson S.K., Glaser R.L., Yates J.R. 3rd, Abmayr S.M., Washburn M.P., Workman J.L. Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions // Science. 2004. Vol. 306. N 5704. P. 2084—2087.Kusch T., Florens L., Macdonald W.H., Swanson S.K., Glaser R.L., Yates J.R. 3rd, Abmayr S.M., Washburn M.P., Workman J.L. Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions // Science. 2004. Vol. 306. N 5704. P. 2084—2087.Laugel V. Cockayne syndrome: the expanding clinical and mutational spectrum // Mech. Ageing Dev. 2013. Vol. 134. N 5—6. P. 161—170.Laugel V. Cockayne syndrome: the expanding clinical and mutational spectrum // Mech. Ageing Dev. 2013. Vol. 134. N 5—6. P. 161—170.Adam S., Polo S.E., Almouzni G. Transcription recovery after DNA damage requires chromatin priming by the H3.3 histone chaperone HIRA // Cell. 2013. Vol. 155. N 1. P. 94—106.Adam S., Polo S.E., Almouzni G. Transcription recovery after DNA damage requires chromatin priming by the H3.3 histone chaperone HIRA // Cell. 2013. Vol. 155. N 1. P. 94—106.Dinant C., Ampatziadis-Michailidis G., Lans H., Tresini M., Lagarou A., Grosbart M., Theil A.F., van Cappellen W.A., Kimura H., Bartek J., Fousteri M., Houtsmuller A.B., Vermeulen W., Marteijn J.A. Enhanced chromatin dynamics by FACT promotes transcriptional restart after UV-induced DNA damage // Mol. Cell. 2013. Vol. 51. N 4. P. 469—79.Dinant C., Ampatziadis-Michailidis G., Lans H., Tresini M., Lagarou A., Grosbart M., Theil A.F., van Cappellen W.A., Kimura H., Bartek J., Fousteri M., Houtsmuller A.B., Vermeulen W., Marteijn J.A. Enhanced chromatin dynamics by FACT promotes transcriptional restart after UV-induced DNA damage // Mol. Cell. 2013. Vol. 51. N 4. P. 469—79.Oksenych V., Zhovmer A., Ziani S., Mari P.O., Eberova J., Nardo T., Stefanini M., Giglia-Mari G., Egly J.M., Coin F. Histone methyltransferase DOT1L drives recovery of gene expression after a genotoxic attack // PLoS Genet. 2013. Vol. 9. N 7. P. e1003611.Oksenych V., Zhovmer A., Ziani S., Mari P.O., Eberova J., Nardo T., Stefanini M., Giglia-Mari G., Egly J.M., Coin F. Histone methyltransferase DOT1L drives recovery of gene expression after a genotoxic attack // PLoS Genet. 2013. Vol. 9. N 7. P. e1003611.Szenker E., Lacoste N., Almouzni G. A developmental requirement for HIRA-dependent H3.3 deposition revealed at gastrulation in Xenopus // Cell Rep. 2012. Vol. 1. N 6. P. 730—740.Szenker E., Lacoste N., Almouzni G. A developmental requirement for HIRA-dependent H3.3 deposition revealed at gastrulation in Xenopus // Cell Rep. 2012. Vol. 1. N 6. P. 730—740.Wilson M.D., Harreman M., Svejstrup J.Q. Ubiquitylation and degradation of elongating RNA polymerase II: the last resort // Biochim. Biophys. Acta. 2013. Vol. 1829. N 1. P. 151—157.Wilson M.D., Harreman M., Svejstrup J.Q. Ubiquitylation and degradation of elongating RNA polymerase II: the last resort // Biochim. Biophys. Acta. 2013. Vol. 1829. N 1. P. 151—157.

The authors declare that there are no conflicts of interest present.