Journal
NATURE CELL BIOLOGY
Volume 18, Issue 3, Pages 271-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3303
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Funding
- Worldwide Cancer Research
- MRC Senior Non-Clinical Fellowships
- MRC Grant
- Cancer Research UK Studentship
- Cancer Research and Prevention Institute of Texas (CPRIT) grant [RP110465-P4]
- Medical Research Council [MR/L007665/1, G0902418] Funding Source: researchfish
- Worldwide Cancer Research [07-0922] Funding Source: researchfish
- MRC [MR/L007665/1, G0902418] Funding Source: UKRI
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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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