Abstract
Repair of DNA double-strand breaks (DSBs) via the homologous recombination (HR) pathway is a highly regulated process. A number of proteins that participate in HR are intricately modulated by the cell cycle and chromatin environments of DSBs. Recent studies have revealed a clear impact of transcription on HR in transcribed regions of the genome. Several models have been put forth to explain how the process of transcription and/or its RNA products may influence HR. Here we discuss the results and models from these studies, presenting an emerging view of transcription-coupled DSB repair.
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Aymard, F., Aguirrebengoa, M., Guillou, E., Javierre, B.M., Bugler, B., Arnould, C., Rocher, V., Iacovoni, J.S., Biernacka, A., Skrzypczak, M., Ginalski, K., Rowicka, M., Fraser, P., and Legube, G. (2017). Genomewide mapping of long-range contacts unveils clustering of DNA double-strand breaks at damaged active genes. Nat Struct Mol Biol 24, 353–361.
Aymard, F., Bugler, B., Schmidt, C.K., Guillou, E., Caron, P., Briois, S., Iacovoni, J.S., Daburon, V., Miller, K.M., Jackson, S.P., and Legube, G. (2014). Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks. Nat Struct Mol Biol 21, 366–374.
Batenburg, N.L., Thompson, E.L., Hendrickson, E.A., and Zhu, X.D. (2015). Cockayne syndrome group B protein regulates DNA double-strand break repair and checkpoint activation. EMBO J 34, 1399–1416.
Daugaard, M., Baude, A., Fugger, K., Povlsen, L.K., Beck, H., Sørensen, C.S., Petersen, N.H.T., Sorensen, P.H.B., Lukas, C., Bartek, J., Lukas, J., Rohde, M., and Jäättelä, M. (2012). LEDGF (p75) promotes DNAend resection and homologous recombination. Nat Struct Mol Biol 19, 803–810.
Eidahl, J.O., Crowe, B.L., North, J.A., McKee, C.J., Shkriabai, N., Feng, L., Plumb, M., Graham, R.L., Gorelick, R.J., Hess, S., Poirier, M.G., Foster, M.P., and Kvaratskhelia, M. (2013). Structural basis for high-affinity binding of LEDGF PWWP to mononucleosomes. Nucleic Acids Res 41, 3924–3936.
Francia, S., Michelini, F., Saxena, A., Tang, D., de Hoon, M., Anelli, V., Mione, M., Carninci, P., and d’Adda di Fagagna, F. (2012). Site-specific DICER and DROSHA RNA products control the DNA-damage response. Nature 488, 231–235.
Gao, M., Wei, W., Li, M.M., Wu, Y.S., Ba, Z., Jin, K.X., Li, M.M., Liao, Y.Q., Adhikari, S., Chong, Z., Zhang, T., Guo, C.X., Tang, T.S., Zhu, B.T., Xu, X.Z., Mailand, N., Yang, Y.G., Qi, Y., and Rendtlew Danielsen, J.M. (2014). Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination. Cell Res 24, 532–541.
Guenther, M.G., Levine, S.S., Boyer, L.A., Jaenisch, R., and Young, R.A. (2007). A chromatin landmark and transcription initiation at most promoters in human cells. Cell 130, 77–88.
Hanawalt, P.C., and Spivak, G. (2008). Transcription-coupled DNA repair: two decades of progress and surprises. Nat Rev Mol Cell Biol 9, 958–970.
Iacovoni, J.S., Caron, P., Lassadi, I., Nicolas, E., Massip, L., Trouche, D., and Legube, G. (2010). High-resolution profiling of γH2AX around DNA double strand breaks in the mammalian genome. EMBO J 29, 1446–1457.
Keskin, H., Shen, Y., Huang, F., Patel, M., Yang, T., Ashley, K., Mazin, A.V., and Storici, F. (2014). Transcript-RNA-templated DNA recombination and repair. Nature 515, 436–439.
Marteijn, J.A., Lans, H., Vermeulen, W., and Hoeijmakers, J.H.J. (2014). Understanding nucleotide excision repair and its roles in cancer and ageing. Nat Rev Mol Cell Biol 15, 465–481.
Ohle, C., Tesorero, R., Schermann, G., Dobrev, N., Sinning, I., and Fischer, T. (2016). Transient RNA-DNA hybrids are required for efficient doublestrand break repair. Cell 167, 1001–1013.e7.
Orthwein, A., Noordermeer, S.M., Wilson, M.D., Landry, S., Enchev, R.I., Sherker, A., Munro, M., Pinder, J., Salsman, J., Dellaire, G., Xia, B., Peter, M., and Durocher, D. (2015). A mechanism for the suppression of homologous recombination in G1 cells. Nature 528, 422–426.
Pradeepa, M.M., Sutherland, H.G., Ule, J., Grimes, G.R., and Bickmore, W.A. (2012). Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing. PLoS Genet 8, e1002717.
Storici, F., Bebenek, K., Kunkel, T.A., Gordenin, D.A., and Resnick, M.A. (2007). RNA-templated DNA repair. Nature 447, 338–341.
Tantin, D. (1998). RNA polymerase II elongation complexes containing the Cockayne syndrome group B protein interact with a molecular complex containing the transcription factor IIH components xeroderma pigmentosum B and p62. J Biol Chem 273, 27794–27799.
Vermeulen, W., and Fousteri, M. (2013). Mammalian transcription-coupled excision repair. Cold Spring Harb Perspect Biol 5, a012625.
Wang, Q., and Goldstein, M. (2016). Small RNAs recruit chromatin-modifying enzymes MMSET and Tip60 to reconfigure damaged DNA upon double-strand break and facilitate repair. Cancer Res 76, 1904–1915.
Wei, L., Nakajima, S., Böhm, S., Bernstein, K.A., Shen, Z., Tsang, M., Levine, A.S., and Lan, L. (2015). DNA damage during the G0/G1 phase triggers RNA-templated, Cockayne syndrome B-dependent homologous recombination. Proc Natl Acad Sci USA 112, E3495–E3504.
Wei, W., Ba, Z., Gao, M., Wu, Y., Ma, Y., Amiard, S., White, C.I., Rendtlew Danielsen, J.M., Yang, Y.G., and Qi, Y. (2012). A role for small RNAs in DNA double-strand break repair. Cell 149, 101–112.
Xiang, Y., Laurent, B., Hsu, C.H., Nachtergaele, S., Lu, Z., Sheng, W., Xu, C., Chen, H., Ouyang, J., Wang, S., Ling, D., Hsu, P.H., Zou, L., Jambhekar, A., He, C., and Shi, Y. (2017). RNA m6A methylation regulates the ultraviolet-induced DNA damage response. Nature 543, 573–576.
Acknowledgements
This work was supported by NIH grants (GM076388 and CA197779 to Lee Zou., GM118833 to Li Lan).
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Ouyang, J., Lan, L. & Zou, L. Regulation of DNA break repair by transcription and RNA. Sci. China Life Sci. 60, 1081–1086 (2017). https://doi.org/10.1007/s11427-017-9164-1
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DOI: https://doi.org/10.1007/s11427-017-9164-1