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Elife January 1, 2020; 9

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

Zhu S , Paydar M , Wang F , Li Y , Wang L , Barrette B , Bessho T , Kwok BH , Peng A .

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.

PubMed ID: 31951198
PMC ID: PMC7012618
Article link: Elife
Grant support: [+]

Species referenced: Xenopus
Genes referenced: atm chek1 h2ax kif2c mbp parp1

Article Images: [+] show captions
References [+] :
Akoumianaki, Nucleocytoplasmic shuttling of soluble tubulin in mammalian cells. 2009, Pubmed