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Nat Commun. 2017 Jun 12;8:15751. doi: 10.1038/ncomms15751.

The anaphase promoting complex impacts repair choice by protecting ubiquitin signalling at DNA damage sites.

Ha K1,2,3, Ma C4, Lin H3, Tang L1,2, Lian Z5, Zhao F6, Li JM7, Zhen B1,2, Pei H1,2, Han S5, Malumbres M8, Jin J7, Chen H1,2, Zhao Y6, Zhu Q4, Zhang P1,2,3.

Author information

National Center for Protein Sciences Beijing, Life Sciences Park, Beijing 102206, China.
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
Department of Medical Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710004, China.
Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, China.
National Center for International Research of Biological Targeting Diagnosis and Therapy, and Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Guangxi 530021, China.
Department of Biochemistry and Molecular Biology, University of Texas Health Sciences Center, Houston, Texas 77030, USA.
Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, Madrid, Spain.


Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). While HDR can only occur in S/G2, NHEJ can happen in all cell cycle phases (except mitosis). How then is the repair choice made in S/G2 cells? Here we provide evidence demonstrating that APCCdh1 plays a critical role in choosing the repair pathways in S/G2 cells. Our results suggest that the default for all DSBs is to recruit 53BP1 and RIF1. BRCA1 is blocked from being recruited to broken ends because its recruitment signal, K63-linked poly-ubiquitin chains on histones, is actively destroyed by the deubiquitinating enzyme USP1. We show that the removal of USP1 depends on APCCdh1 and requires Chk1 activation known to be catalysed by ssDNA-RPA-ATR signalling at the ends designated for HDR, linking the status of end processing to RIF1 or BRCA1 recruitment.

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