Role for RIF1-interacting partner DDX1 in BLM recruitment to DNA double-strand breaks |
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| Affiliation: | 1. Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton Alberta T6G 1Z2, Canada;2. Department of Biochemistry, University of Alberta Edmonton Alberta, Canada;1. Department of General Surgery, Zhujiang Hospital of Southern Medical University, NO. 253 Guangzhou Industrial Avenue, Guangzhou 510282, Guangdong Province, China;2. Affiliated Cancer Hospital & Institute of Guangzhou Medical University, NO. 78 Hengzhigang Road, Guangzhou 510095, Guangdong, China;1. Department of Applied Mathematics, Department of Physics and Astronomy, University of Western Ontario, London, Ontario N6A 5B7, Canada;2. Perimeter Institute for Theoretical Physics, Waterloo, Ontario N2J 2W9, Canada;1. Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, NT, Hong Kong SAR, China;2. School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, Hong Kong SAR, China;3. Center of Breast Diseases, Peking University People’s Hospital, Peking University, Beijing, China;1. Department of Physics, Kent State University, Kent, Ohio;2. Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland;3. Department of Physics and Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, Illinois;1. Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland;2. Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic;3. Institute of Biochemistry, ETH Zurich, Otto-Stern-Weg 3, 8093 Zurich, Switzerland;1. Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China;2. Digestive Department, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China;3. Department Surgery, Hubei Province Nanzhang County Hospital of Traditional Chinese Medicine, Xiangyang 441021, Hubei, China;4. Pathology Department, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China |
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| Abstract: | ![]()
Human Rap1-interacting factor 1 (RIF1) is an important player in the repair of DNA double strand breaks (DSBs). RIF1 acts downstream of 53BP1, with well-documented roles in class switch recombination in B-cells and inhibition of end resection initiation in BRCA1-defective cells. Here, we report that DEAD Box 1 (DDX1), a RNA helicase also implicated in DSB repair, interacts with RIF1, with co-localization of DDX1 and RIF1 observed throughout interphase. Recruitment of DDX1 to DSBs is dependent on RIF1, with RIF1 depletion abolishing DDX1-mediated facilitation of homologous recombination at DSBs. As previously demonstrated for RIF1, DDX1 is also required for chromatin loading of Bloom syndrome helicase (BLM) to ionizing radiation-induced DSBs, a RIF1-related activity that is independent of 53BP1. We show that DDX1 and RIF1 have different nucleic acid requirements for accumulation at DSBs, with RNA-DNA hybrids required for DDX1 accrual at DSBs, and single-strand RNA required for accumulation of RIF1 at these sites. Our data suggest both convergent and divergent roles for DDX1 and RIF1 in DSB repair, and may help explain why RIF1 depletion does not fully mimic 53BP1 ablation in the restoration of homologous recombination defects in BRCA1-deficient cells. |
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| Keywords: | DNA double strand break repair RNA helicase Homologous recombination Non-homologous end joining Protein-protein interaction |
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