Breast cancer proteins PALB2 and BRCA2 stimulate polymerase η in recombination-associated DNA Synthesis At Blocked Replication Forks

Rémi Buisson, Joshi Niraj, Joris Pauty, Ranjan Maity, Weixing Zhao, Yan Coulombe, Patrick Sung, Jean Yves Masson

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

One envisioned function of homologous recombination (HR) is to find a template for DNA synthesis from the resected 3'-OH molecules that occur during double-strand break (DSB) repair at collapsed replication forks. However, the interplay between DNA synthesis and HR remains poorly understood in higher eukaryotic cells. Here, we reveal functions for the breast cancer proteins BRCA2 and PALB2 at blocked replication forks and show a role for these proteins in stimulating polymerase η (Polη) to initiate DNA synthesis. PALB2, BRCA2, and Polη colocalize at stalled or collapsed replication forks after hydroxyurea treatment. Moreover, PALB2 and BRCA2 interact with Polη and are required to sustain the recruitment of Polη at blocked replication forks. PALB2 and BRCA2 stimulate Polη-dependent DNA synthesis on D loop substrates. We conclude that PALB2 and BRCA2, in addition to their functions in D loop formation, play crucial roles in the initiation of recombination-associated DNA synthesis by Polη-mediated DNA repair.

Original languageEnglish (US)
Pages (from-to)553-564
Number of pages12
JournalCell Reports
Volume6
Issue number3
DOIs
StatePublished - Feb 13 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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