PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts.pdf (1.85 MB)
PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts
journal contributionposted on 2023-06-10, 00:43 authored by Ann Liza Piberger, Akhil Bowry, Richard D W Kelly, Alexandra K Walker, Daniel González-Acosta, Laura BaileyLaura Bailey, Aidan DohertyAidan Doherty, Juan Méndez, Joanna R Morris, Helen E Bryant, Eva Petermann
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.
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- Sussex Centre for Genome Damage Stability Publications
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