TY - JOUR
T1 - RAD51 bypasses the CMG helicase to promote replication fork reversal
AU - Liu, Wenpeng
AU - Saito, Yuichiro
AU - Jackson, Jessica
AU - Bhowmick, Rahul
AU - Kanemaki, Masato T.
AU - Vindigni, Alessandro
AU - Cortez, David
N1 - Funding Information:
This work was funded by the following: National Institutes of Health grant R01GM116616 (to D.C.); Breast Cancer Research Foundation Grant (to D.C.); National Cancer Institute grant R01CA237263 (to A.V.); National Cancer Institute grant R01CA248526 (to A.V.); US Department of Defense (DOD) Breast Cancer Research Program (BRCP) Expansion Award BC191374 (to A.V.); JSPS KAKENHI grant JP21K15021 (to Y.S.); JSPS KAKENHI grants JP21H04719 and JP22H04703 (to M.T. K.); JST CREST program JPMJCR21E6 (to M.T.K.).
Publisher Copyright:
© 2023 The Authors.
PY - 2023/4/28
Y1 - 2023/4/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85159242036&partnerID=8YFLogxK
U2 - 10.1126/science.add7328
DO - 10.1126/science.add7328
M3 - Article
C2 - 37104614
AN - SCOPUS:85159242036
SN - 0036-8075
VL - 380
SP - 382
EP - 387
JO - Science
JF - Science
IS - 6643
ER -