https://scholars.lib.ntu.edu.tw/handle/123456789/638110
標題: | RAD51 paralogs synergize with RAD51 to protect reversed forks from cellular nucleases | 作者: | Guh, Chia-Lun Lei, Kai-Hang Chen, Yi-An Jiang, Yi-Zhen Chang, Hao-Yen Liaw, Hungjiun HUNG-WEN LI Yen, Hsin-Yung HUNG-YUAN CHI |
公開日期: | 27-十一月-2023 | 出版社: | Oxford University Press | 卷: | 51 | 期: | 21 | 起(迄)頁: | 11717 - 11731 | 來源出版物: | Nucleic acids research | 摘要: | Fork reversal is a conserved mechanism to prevent stalled replication forks from collapsing. Formation and protection of reversed forks are two crucial steps in ensuring fork integrity and stability. Five RAD51 paralogs, namely, RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3, which share sequence and structural similarity to the recombinase RAD51, play poorly defined mechanistic roles in these processes. Here, using purified BCDX2 (RAD51BCD-XRCC2) and CX3 (RAD51C-XRCC3) complexes and in vitro reconstituted biochemical systems, we mechanistically dissect their functions in forming and protecting reversed forks. We show that both RAD51 paralog complexes lack fork reversal activities. Whereas CX3 exhibits modest fork protection activity, BCDX2 significantly synergizes with RAD51 to protect DNA against attack by the nucleases MRE11 and EXO1. DNA protection is contingent upon the ability of RAD51 to form a functional nucleoprotein filament on DNA. Collectively, our results provide evidence for a hitherto unknown function of RAD51 paralogs in synergizing with RAD51 nucleoprotein filament to prevent degradation of stressed replication forks. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/638110 | ISSN: | 03051048 | DOI: | 10.1093/nar/gkad856 |
顯示於: | 生化科學研究所 |
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