Kinesin Kif2C in regulation of DNA double strand break dynamics and repair

Songli Zhu, Mohammadjavad Paydar, Feifei Wang, Yanqiu Li, Ling Wang, Benoit Barrette, Tadayoshi Bessho, Benjamin H. Kwok, Aimin Peng

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Article numbere53402
JournaleLife
Volume9
DOIs
StatePublished - Jan 2020

Keywords

  • DNA repair
  • Dynamics
  • Kif2C
  • MCAK
  • Mobility

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Zhu, S., Paydar, M., Wang, F., Li, Y., Wang, L., Barrette, B., Bessho, T., Kwok, B. H., & Peng, A. (2020). Kinesin Kif2C in regulation of DNA double strand break dynamics and repair. eLife, 9, [e53402]. https://doi.org/10.7554/eLife.53402