2026-06-30T02:01:38Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/121772024-11-29T16:08:26Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Piberger, Ann Liza author Bowry, Akhil author Kelly, Richard D W author Walker, Alexandra K author Gonzalez-Acosta, Daniel author Bailey, Laura J author Doherty, Aidan J author Méndez, Juan author Morris, Joanna R author Bryant, Helen E author Petermann, Eva author Mendez, Juan author 2020-11-11 Stalled replication forks can be restarted and repaired by RAD51-mediated homologous recombination (HR), but HR can also perform post-replicative repair after bypass of the obstacle. Bulky DNA adducts are important replication-blocking lesions, but it is unknown whether they activate HR at stalled forks or behind ongoing forks. Using mainly BPDE-DNA adducts as model lesions, we show that HR induced by bulky adducts in mammalian cells predominantly occurs at post-replicative gaps formed by the DNA/RNA primase PrimPol. RAD51 recruitment under these conditions does not result from fork stalling, but rather occurs at gaps formed by PrimPol re-priming and resection by MRE11 and EXO1. In contrast, RAD51 loading at double-strand breaks does not require PrimPol. At bulky adducts, PrimPol promotes sister chromatid exchange and genetic recombination. Our data support that HR at bulky adducts in mammalian cells involves post-replicative gap repair and define a role for PrimPol in HR-mediated DNA damage tolerance. Nat Commun.2020 ;11(1):5863. 10.1038/s41467-020-19570-7 2041-1723 Nature communications 33203852 http://hdl.handle.net/20.500.12105/12177 PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts.