Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Nature communications, 2020-11, Vol.11 (1), p.5863-14, Article 5863

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.