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DOI10.1073/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
ISSN0027-8424
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
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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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