Publication: RIF1 is essential for 53BP1-dependent nonhomologous end joining and suppression of DNA double-strand break resection
Authors
Chapman, J Ross ; Barral, Patricia ; Vannier, Jean-Baptiste ; Borel, Valerie ; Steger, Martin ; Tomas-Loba, Antonia ; Sartori, Alessandro A ; Adams, Ian R ; Batista, Facundo D ; Boulton, Simon J
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Publisher
Cell Press
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DOI
https://doi.org/10.1016/j.molcel.2013.01.002
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info:eu-repo/semantics/article
Description
©<2013>. This manuscript version is made available under the CC-BY-NC-ND license http://creativecommons.org/licenses/by-nc-nd/4.0/
This document is the Published, version of a Published Work that appeared in final form in [Molecular Cell]. To access the final edited and published work see [https://doi.org/10.1016/j.molcel.2013.01.002]
Abstract
The appropriate execution of DNA double-strand
break (DSB) repair is critical for genome stability
and tumor avoidance. 53BP1 and BRCA1 directly
influence DSB repair pathway choice by regulating
50 end resection, but how this is achieved remains
uncertain. Here we report that Rif1 / mice are
severely compromised for 53BP1-dependent class
switch recombination (CSR) and fusion of dysfunc-
tional telomeres. The inappropriate accumulation of
RIF1 at DSBs in S phase is antagonized by BRCA1,
and deletion of Rif1 suppresses toxic nonhomolo-
gous end joining (NHEJ) induced by PARP inhibition
in Brca1-deficient cells. Mechanistically, RIF1 is re-
cruited to DSBs via the N-terminal phospho-SQ/TQ
domain of 53BP1, and DSBs generated by ionizing
radiation or during CSR are hyperresected in the
absence of RIF1. Thus, RIF1 and 53BP1 cooperate
to block DSB resection to promote NHEJ in G1,
which is antagonized by BRCA1 in S phase to
ensure a switch of DSB repair mode to homologous
recombination.
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Citation
Molecular Cell 49(5):858-871, 2013
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