Institute for Research in Immunology and Cancer (IRIC), Département de médecine, Université de Montréal, Montréal, Canada
Feifei Wang
Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Omaha, United States; Institute of Physical Science and Information Technology, Anhui University, Hefei, China
Yanqiu Li
Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Omaha, United States
Ling Wang
Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Omaha, United States
Benoit Barrette
Institute for Research in Immunology and Cancer (IRIC), Département de médecine, Université de Montréal, Montréal, Canada
Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, United States
DNA double strand breaks (DSBs) have detrimental effects on cell survival and genomic stability, and are related to cancer and other human diseases. In this study, we identified microtubule-depolymerizing kinesin Kif2C as a protein associated with DSB-mimicking DNA templates and known DSB repair proteins in Xenopus egg extracts and mammalian cells. The recruitment of Kif2C to DNA damage sites was dependent on both PARP and ATM activities. Kif2C knockdown or knockout led to accumulation of endogenous DNA damage, DNA damage hypersensitivity, and reduced DSB repair via both NHEJ and HR. Interestingly, Kif2C depletion, or inhibition of its microtubule depolymerase activity, reduced the mobility of DSBs, impaired the formation of DNA damage foci, and decreased the occurrence of foci fusion and resolution. Taken together, our study established Kif2C as a new player of the DNA damage response, and presented a new mechanism that governs DSB dynamics and repair.
