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.

中文翻译：

---

Kinesin Kif2C在调节DNA双链断裂动力学和修复中的作用

DNA双链断裂（DSB）对细胞存活和基因组稳定性有不利影响，并且与癌症和其他人类疾病有关。在这项研究中，我们确定微管解聚的驱动蛋白Kif2C是与模仿DSB的DNA模板相关的蛋白，并且是爪蟾中已知的DSB修复蛋白。卵提取物和哺乳动物细胞。将Kif2C募集至DNA损伤位点取决于PARP和ATM活动。Kif2C的敲低或敲除导致内源性DNA损伤的积累，DNA损伤的超敏性以及通过NHEJ和HR引起的DSB修复减少。有趣的是，Kif2C耗竭或抑制其微管解聚酶活性，降低了DSB的迁移率，削弱了DNA损伤灶的形成，并减少了灶融合和分离的发生。综上所述，我们的研究使Kif2C成为DNA损伤反应的新参与者，并提出了一种控制DSB动态和修复的新机制。