Homologous Recombination and Replication Fork Protection: BRCA2 and More!

Overview

Journal Cold Spring Harb Symp Quant Biol

Specialty Biology

Date 2018 Apr 25

PMID 29686033

Citations 41

Authors

Weiran Feng

Maria Jasin

Affiliations

Soon will be listed here.

Abstract

BRCA2 is a breast and ovarian tumor suppressor that guards against genome instability, a hallmark of cancer. Significant progress has been made in improving our understanding of BRCA2 function from biochemical, cellular, and mouse studies. The knowledge gained has been actively exploited to develop therapeutic strategies, including PARP inhibition, which has shown promising clinical outcomes. Recently, tremendous excitement has been generated by the findings of the roles of BRCA2 and other proteins in suppressing replication stress through homologous recombination and in the protection of stalled replication forks. Processes such as mitotic DNA synthesis and fork reversal have taken center stage in these studies. Here, we discuss our recent findings in the context of these advances.

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BRCA2 stabilises RAD51 and DMC1 nucleoprotein filaments through a conserved interaction mode.

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DMC1 and RAD51 bind FxxA and FxPP motifs of BRCA2 via two separate interfaces.

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