研究报告

RAD51调控REV1参与DNA双链断裂修复

展开
  • 1. 中国科学院北京基因组研究所,中国科学院精准基因组医学重点实验室,北京 100101
    2. 中国科学院大学,北京 100049
    3. 中国科学院未来技术学院,北京 101408
黄敏,博士研究生,专业方向:生物化学与分子生物学。E-mail: huangmin@big.ac.cn

收稿日期: 2018-06-29

  修回日期: 2018-10-19

  网络出版日期: 2018-10-30

基金资助

国家重点研发计划项目(2018YFA0108500);国家自然科学基金项目(81630078);国家自然科学基金项目(31471331)

RAD51 regulates REV1 recruitment to DNA double-strand
break sites

Expand
  • 1. CAS Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
    2. University of Chinese Academy of Sciences, Beijing 100049, China
    3. School of Future Technology, Chinese Academy of Sciences, Beijing 101408, China

Received date: 2018-06-29

  Revised date: 2018-10-19

  Online published: 2018-10-30

Supported by

Supported by the National Key Research and Development Program of China(2018YFA0108500);the National Natural Science Foundation of China(81630078);the National Natural Science Foundation of China(31471331)

摘要

REV1是跨损伤聚合酶Y家族的重要成员之一,它不仅作为支架蛋白介导Y家族聚合酶招募至损伤位点完成跨损伤DNA合成(translesion DNA synthesis, TLS),还可利用自身的dCMP转移酶活性在一些损伤位点对侧整合dCMP参与TLS。此外,REV1也被报导参与调控同源重组修复。为进一步探讨REV1互作蛋白RAD51和RAD51C在其参与的同源重组修复通路中的调控作用,本研究采用脉冲氮激光微辐射实验,发现RAD51可调控REV1到双链断裂位点的募集。同时,免疫荧光实验结果证明REV1也反过来影响RAD51应答CPT损伤。然而敲低RAD51C并不影响REV1到DNA双链断裂位点的招募。结果表明,REV1和RAD51在HR通路中存在彼此相互调控的关系。

本文引用格式

黄敏,杨业然,孙晓艳,张婷,郭彩霞 . RAD51调控REV1参与DNA双链断裂修复[J]. 遗传, 2018 , 40(11) : 1007 -1014 . DOI: 10.16288/j.yczz.18-176

Abstract

REV1 is one of the major Y-family DNA polymerases. It not only functions as a scaffold protein to mediate other specialized DNA polymerases to sites of lesions, but also inserts deoxycytidine across the lesion strand during translesion DNA synthesis (TLS). Meanwhile, REV1 has been reported to be involved in homologous recombination (HR) repair. Here we further explore the roles of REV1-interacting proteins RAD51 and RAD51C in REV1-mediated DNA double-strand break (DSB) repair. We found that RAD51 but not RAD51C regulates REV1 recruitment to DSB sites via pulsed laser microirradiation. Interestingly, immunofluorescence staining exhibits that REV1 also regulates RAD51 focus formation in response to CPT treatment. These results suggest that REV1 and RAD51 might be mutually dependent on each other in the REV1-related HR pathway.

参考文献

[1] Sale JE, Lehmann AR, Woodgate R . Y-family DNA polymerases and their role in tolerance of cellular DNA damage . Nat Rev Mol Cell Biol, 2012,13(3):141-152.
[2] Guo CC, Kosarek-Stancel JN, Tang T-S, Friedberg EC . Y-family DNA polymerases in mammalian cells . Cell Mol Life Sci, 2009,66(14):2363-2381.
[3] Vaisman A, Woodgate R . Translesion DNA polymerases in eukaryotes: what makes them tick? Crit Rev Biochem Mol Biol, 2017,52(3):274-303.
[4] Yang W . An overview of Y-Family DNA polymerases and a case study of human DNA polymerase η . Biochemistry, 2014,53(17):2793-2803.
[5] Ma XL, Liu HH, Li J, Wang Y, Ding YH, Shen H, Yang Y, Sun C, Huang M, Tu Y, Liu Y, Zhao Y, Dong MQ, Xu P, Tang TS, Guo C . Polη O-GlcNAcylation governs genome integrity during translesion DNA synthesis . Nat Commun, 2017,8(1):1941.
[6] Huang M, Zhou B, Gong J, Xing L, Ma X, Wang F, Wu W, Shen H, Sun C, Zhu X, Yang Y, Sun Y, Liu Y, Tang TS, Guo C . RNA-splicing factor SART3 regulates translesion DNA synthesis . Nucleic Acids Res, 2018,46(9):4560-4574.
[7] Lehmann AR . New functions for Y family polymerases . Mol Cell, 2006,24(4):493-495.
[8] Zhang X, Lv L, Chen Q, Yuan F, Zhang T, Yang Y, Zhang H, Wang Y, Jia Y, Qian L, Chen B, Zhang Y, Friedberg EC, Tang TS, Guo C . Mouse DNA polymerase kappa has a functional role in the repair of DNA strand breaks . DNA Repair (Amst), 2013,12(5):377-388.
[9] McIlwraith MJ, Vaisman A, Liu Y, Fanning E, Woodgate R, West SC . Human DNA polymerase eta promotes DNA synthesis from strand invasion intermediates of homologous recombination . Mol Cell, 2005,20(5):783-792.
[10] Okada T, Sonoda E, Yoshimura M, Kawano Y, Saya H, Kohzaki M, Takeda S . Multiple roles of vertebrate REV genes in DNA repair and recombination . Mol Cell Biol, 2005,25(14):6103-6111.
[11] Hirano Y, Sugimoto K . ATR homolog Mec1 controls association of DNA polymerase zeta-Rev1 complex with regions near a double-strand break . Curr Biol, 2006,16(6):586-590.
[12] Kane DP, Shusterman M, Rong Y , Yang YG.Competition between replicative and translesion polymerases during homologous recombination repair in Drosophila. PLoS Genet, 2012,8(4):e1002659.
[13] Sharma S, Hicks JK, Chute CL, Brennan JR, Ahn JY, Glover TW, Canman CE . REV1 and polymerase zeta facilitate homologous recombination repair . Nucleic Acids Res, 2012,40(2):682-691.
[14] Yang Y, Liu Z, Wang F, Temviriyanukul P, Ma X, Tu Y, Lv L, Lin YF, Huang M, Zhang T, Pei H, Chen BP Jansen JG, de Wind N, Fischhaber PL, Friedberg EC, Tang TS, Guo C. FANCD2 and REV1 cooperate in the protection of nascent DNA strands in response to replication stress . Nucleic Acids
文章导航

/