2. Academic Validation
  3. EXD2 promotes homologous recombination by facilitating DNA end resection

EXD2 promotes homologous recombination by facilitating DNA end resection

  • Nat Cell Biol. 2016 Mar;18(3):271-280. doi: 10.1038/ncb3303.
Ronan Broderick # 1,  Jadwiga Nieminuszczy # 1,  Hannah T Baddock 2,  Rajashree Deshpande 3,  Opher Gileadi 2,  Tanya T Paull 3,  Peter J McHugh 1,  Wojciech Niedzwiedz 1
Affiliations

Affiliations

  • 1 Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
  • 2 Structural Genomics Consortium, Old Road Campus Research Building, Roosevelt Drive, University of Oxford, Oxford OX3 7DQ, UK.
  • 3 The Howard Hughes Medical Institute and Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
  • # Contributed equally.
PMID: 26807646 DOI: 10.1038/ncb3303
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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