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- Title
PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts.
- Authors
Piberger, Ann Liza; Bowry, Akhil; Kelly, Richard D. W.; Walker, Alexandra K.; González-Acosta, Daniel; Bailey, Laura J.; Doherty, Aidan J.; Méndez, Juan; Morris, Joanna R.; Bryant, Helen E.; Petermann, Eva
- Abstract
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. Bulky DNA adducts are important replication-blocking lesions. Here the authors reveal that homologous recombination at bulky adducts in mammalian cells involves post-replicative gap repair in a PrimPol dependent manner.
- Subjects
DNA adducts; SINGLE-stranded DNA; RECOMBINANT DNA; SISTER chromatid exchange; HOMOLOGOUS recombination; DNA damage
- Publication
Nature Communications, 2020, Vol 11, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-19570-7