Vertebrate mammals express a protein called Ki-67 which is most widely known as a clinically useful marker of highly proliferative cells. Previous studies of human cells indicated that acute depletion of Ki-67 can elicit a delay at the G1/S boundary of the cell cycle, dependent on induction of the checkpoint protein p21. Consistent with those observations, we show here that acute Ki-67 depletion causes hallmarks of DNA damage, and the damage occurs even in the absence of checkpoint signaling. This damage is not observed in cells traversing S phase but is instead robustly detected in mitotic cells. The C-terminal chromatin binding domain of Ki-67 is necessary and sufficient to protect cells from this damage. We also observe synergistic effects when Ki-67 and p53 are simultaneously depleted, resulting in increased levels of chromosome bridges at anaphase, followed by the appearance of micronuclei. Therefore, these studies identify the C-terminus of Ki-67 as an important module for genome stability.

中文翻译：

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Ki-67的染色质结合域与p53一起保护人类染色体免受有丝分裂损害

脊椎动物哺乳动物表达一种称为Ki-67的蛋白质，该蛋白质被广泛称为高度增殖细胞的临床有用标记。先前对人类细胞的研究表明，Ki-67的急性耗竭可引起细胞周期G1 / S边界的延迟，这取决于对检查点蛋白p21的诱导。与这些观察结果一致，我们在这里表明，急性Ki-67耗竭会引起DNA损伤的标志，即使在没有检查站信号的情况下，损伤也会发生。在横穿S期的细胞中未观察到这种损害，而是在有丝分裂细胞中被稳健地检测到。Ki-67的C端染色质结合结构域对于保护细胞免受这种损害是必要和充分的。当Ki-67和p53同时耗尽时，我们还会观察到协同效应，导致后期的染色体桥水平增加，随后出现微核。因此，这些研究确定了Ki-67的C端是基因组稳定性的重要模块。