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DOI | 10.1073/pnas.2021998118 |
The chromatin-binding domain of Ki-67 together with p53 protects human chromosomes from mitotic damage | |
Garwain O.; Sun X.; Iyer D.R.; Li R.; Zhu L.J.; Kaufman P.D. | |
发表日期 | 2021 |
ISSN | 0027-8424 |
卷号 | 118期号:32 |
英文摘要 | 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. © 2021 National Academy of Sciences. All rights reserved. |
英文关键词 | Chromatin; DNA damage; Mitosis |
语种 | 英语 |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/238835 |
作者单位 | Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, United States |
推荐引用方式 GB/T 7714 | Garwain O.,Sun X.,Iyer D.R.,et al. The chromatin-binding domain of Ki-67 together with p53 protects human chromosomes from mitotic damage[J],2021,118(32). |
APA | Garwain O.,Sun X.,Iyer D.R.,Li R.,Zhu L.J.,&Kaufman P.D..(2021).The chromatin-binding domain of Ki-67 together with p53 protects human chromosomes from mitotic damage.Proceedings of the National Academy of Sciences of the United States of America,118(32). |
MLA | Garwain O.,et al."The chromatin-binding domain of Ki-67 together with p53 protects human chromosomes from mitotic damage".Proceedings of the National Academy of Sciences of the United States of America 118.32(2021). |
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