PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts

Research output: Contribution to journalArticlepeer-review

Authors

  • Daniel Gonzalez-Acosta
  • Laura Bailey
  • A Doherty
  • Juan Mendez
  • Helen E Bryant
  • Eva Petermann

Colleges, School and Institutes

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.

Details

Original languageEnglish
Article number5863
JournalNature Communications
Volume11
Publication statusPublished - 17 Nov 2020