DNA损伤响应（DDR）在间期期间涉及积极的信号传递和修复，以确保基因组的稳定性。然而，有关有丝分裂细胞如何对DNA损伤作出反应仍知之甚少。支持相关的活体/固定细胞显微镜技术，发现无论它们与DNA如何相互作用，暴露于几种癌症化疗化合物下的有丝分裂细胞都会获得和信号传递DNA损伤。对有丝分裂期间DNA损伤的深入分析揭示了螺旋纤维装配检查点（SAC）依赖的、但不依赖共济失调毛细血管扩张症异型蛋白质（ATM）的有丝分裂延迟。这种延迟是由于染色体错位存在，最终满足了SAC并错分离，导致微核形成。在机制上，表明有丝分裂DNA损伤由染色体运动蛋白引起的臂抛出力导致极性染色体错分离。重要的是，除了由拓扑异构酶II抑制剂依托泊甙诱导的DNA损伤外，这种结果独立于它对着丝粒微管稳定性的一般影响。在全癌细胞系模型中进行的集落形成实验表明，根据损伤的性质和程度，有丝分裂DNA损伤会导致不同的细胞毒性效应。总之，这些发现揭示并引起关注的是，治疗性DNA损伤方案可能通过一种与染色体运动蛋白介导的极性染色体错分离的惊人联系来促进基因组不稳定性。

DNA damage response (DDR) during interphase involves active signaling and repair to ensure genomic stability. However, how mitotic cells respond to DNA damage remains poorly understood. Supported by correlative live-/fixed-cell microscopy, it was found that mitotic cells exposed to several cancer chemotherapy compounds acquire and signal DNA damage, regardless of how they interact with DNA. In-depth analysis upon DNA damage during mitosis revealed a spindle assembly checkpoint (SAC)-dependent, but ataxia telangiectasia mutated-independent, mitotic delay. This delay was due to the presence of misaligned chromosomes that ultimately satisfy the SAC and missegregate, leading to micronuclei formation. Mechanistically, it is shown that mitotic DNA damage causes missegregation of polar chromosomes due to the action of arm-ejection forces by chromokinesins. Importantly, with the exception of DNA damage induced by etoposide-a topoisomerase II inhibitor-this outcome was independent of a general effect on kinetochore microtubule stability. Colony formation assays in pan-cancer cell line models revealed that mitotic DNA damage causes distinct cytotoxic effects, depending on the nature and extent of the damage. Overall, these findings unveil and raise awareness that therapeutic DNA damage regimens may contribute to genomic instability through a surprising link with chromokinesin-mediated missegregation of polar chromosomes in cancer cells.