EXD2 promotes homologous recombination by facilitating DNA end resection

Nature Cell Biology
Ronan BroderickWojciech Niedzwiedz

Abstract

Repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is critical for survival and genome stability of individual cells and organisms, but also contributes to the genetic diversity of species. A vital step in HR is MRN-CtIP-dependent end resection, which generates the 3' single-stranded DNA overhangs required for the subsequent strand exchange reaction. Here, we identify EXD2 (also known as EXDL2) as an exonuclease essential for DSB resection and efficient HR. EXD2 is recruited to chromatin in a damage-dependent manner and confers resistance to DSB-inducing agents. EXD2 functionally interacts with the MRN complex to accelerate resection through its 3'-5' exonuclease activity, which efficiently processes double-stranded DNA substrates containing nicks. Finally, we establish that EXD2 stimulates both short- and long-range DSB resection, and thus, together with MRE11, is required for efficient HR. This establishes a key role for EXD2 in controlling the initial steps of chromosomal break repair.

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Citations

May 14, 2016·Acta Biochimica Et Biophysica Sinica·Sharad C Paudyal, Zhongsheng You
Jun 2, 2016·Cell Cycle·Jadwiga NieminuszczyWojciech Niedzwiedz
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Sep 3, 2020·Cell Metabolism·Hana AntonickaEric A Shoubridge
Jul 30, 2021·Frontiers in Cell and Developmental Biology·Stephanie M AckersonJason A Stewart
Oct 29, 2019·Biochemistry·Chang-Mo Yoo, Hyun-Woo Rhee

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Methods Mentioned

BETA
co-immunoprecipitations
chromosomal aberrations
transfection
PCR
Assay
co-immunoprecipitation
immunoprecipitation
flow cytometry
gel filtration

Software Mentioned

Huygens Professional ( Scientific Volume Imaging )
FIJI
MASCOT
Prism
Excel
Optimized
ImageJ
PAWS
Summit
Zen

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