@article{2e0aa63a28ff486fb1a102c9409d16a2,
title = "Kinesin Kif2C in regulation of DNA double strand break dynamics and repair",
abstract = "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.",
keywords = "DNA repair, Dynamics, Kif2C, MCAK, Mobility",
author = "Songli Zhu and Mohammadjavad Paydar and Feifei Wang and Yanqiu Li and Ling Wang and Benoit Barrette and Tadayoshi Bessho and Kwok, {Benjamin H.} and Aimin Peng",
note = "Funding Information: supported by the Nebraska Research Initiative, the Fred and Pamela Buffett Cancer Center Funding Information: supported by NIH grant CA172574 to Funding Information: We thank Dr. Jay Reddy (University of Nebraska-Lincoln) for technical support with X-ray irradiation, Christian Charbonneau of the Bioimaging facility of the Institute for Research in Immunology and Cancer (IRIC, Universit? de Montr?al) for technical support with high-resolution microscopy, and Dr. Greg Oakley (University of Nebraska Medical Center) for stimulating discussions. The UNMC Advanced Microscopy Core Facility was supported by the Nebraska Research Initiative, the Fred and Pamela Buffett Cancer Center Support Grant (P30CA036727), and an Institutional Development Award (IDeA) from the NIGMS of the NIH (P30GM106397). The IRIC is supported in part by the Canadian Center of Excellence in Commercialization and Research (CECR), the Canada Foundation for Innovation and Fonds de recherche du Qu?bec ? Sant? (FRQS). This work was partially supported by NIH grant CA172574 to A.P., and funding to B.H.K. from the Canadian Institutes of Health Research (CIHR, PJT# 148982 & 152920), Cancer Research Society (CRS), FRQS and the Strategic Project Committee (SPC) of IRIC. Funding Information: NIGMS of the NIH (P30GM106397). The IRIC is supported in part by the Canadian Center Publisher Copyright: {\textcopyright} 2020, eLife Sciences Publications Ltd. All rights reserved.",
year = "2020",
month = jan,
doi = "10.7554/eLife.53402",
language = "English (US)",
volume = "9",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}