2026-06-30T02:01:42Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/121772024-11-29T16:08:26Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
Deutsche Forschungsgemeinschaft (Alemania)
funder
UK Research and Innovation
funder
Medical Research Council (Reino Unido)
funder
Unión Europea. Comisión Europea
funder
Cancer Research UK (Reino Unido)
funder
Wellcome Trust
2021-03-09T14:23:07Z
2021-03-09T14:23:07Z
2020-11-11
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
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.
eng
PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts.
journal article
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