Kinesin Kif2C in regulation of DNA double strand break dynamics and repair
- University of Nebraska Medical Center, United States
- Université de Montréal, Canada
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Mohammadjavad Paydar
Funding
National Institutes of Health (CA172574)
- Aimin Peng
Canadian Institutes of Health Research (148982)
- Benjamin H Kwok
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Wolf-Dietrich Heyer, University of California, Davis, United States
Version history
- Received: November 7, 2019
- Accepted: January 16, 2020
- Accepted Manuscript published: January 17, 2020 (version 1)
- Accepted Manuscript updated: January 21, 2020 (version 2)
- Version of Record published: February 11, 2020 (version 3)
Copyright
© 2020, Zhu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Kinesin Kif2C in regulation of DNA double strand break dynamics and repair
eLife 9:e53402.
https://doi.org/10.7554/eLife.53402
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