RAD51 bypasses the CMG helicase to promote replication fork reversal

被引：36

作者：

Liu, Wenpeng ^{[1
]}

Saito, Yuichiro ^{[2
,6
]}

Jackson, Jessica ^{[3
]}

Bhowmick, Rahul ^{[1
]}

Kanemaki, Masato T. ^{[2
,4
,5
]}

Vindigni, Alessandro ^{[3
]}

Cortez, David ^{[1
]}

机构：

[1] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37237 USA

[2] Res Org Informat & Syst ROIS, Natl Inst Genet, Dept Chromosome Sci, Yata 1111, Mishima, Shizuoka 4118540, Japan

[3] Washington Univ, Sch Med, Dept Med, Div Oncol, St. Louis, MO 63110 USA

[4] Grad Univ Adv Studies SOKENDAI, Dept Genet, Yata 1111, Mishima, Shizuoka 4118540, Japan

[5] Univ Tokyo, Dept Biol Sci, Tokyo 1130033, Japan

[6] Mem Sloan Kettering Canc Ctr, Mol Biol Program, New York, NY 10065 USA

来源：

SCIENCE | 2023年 / 380卷 / 6643期

基金：

美国国家卫生研究院;

关键词：

ATP HYDROLYSIS; DNA-REPAIR; DEGRADATION; BINDING; MUTATIONS; FILAMENTS; RESTART; REGRESSION; STABILITY; ROLES;

D O I：

10.1126/science.add7328

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Replication fork reversal safeguards genome integrity as a replication stress response. DNA translocases and the RAD51 recombinase catalyze reversal. However, it remains unknown why RAD51 is required and what happens to the replication machinery during reversal. We find that RAD51 uses its strand exchange activity to circumvent the replicative helicase, which remains bound to the stalled fork. RAD51 is not required for fork reversal if the helicase is unloaded. Thus, we propose that RAD51 creates a parental DNA duplex behind the helicase that is used as a substrate by the DNA translocases for branch migration to create a reversed fork structure. Our data explain how fork reversal happens while maintaining the helicase in a position poised to restart DNA synthesis and complete genome duplication.

引用

页码：382 / +

页数：6

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