{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Garwain O"],"funding":["HHS | NIH | National Institute of General Medical Sciences"],"pagination":["e2021998118"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8364191"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["118(32)"],"pubmed_abstract":["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."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["The chromatin-binding domain of Ki-67 together with p53 protects human chromosomes from mitotic damage."],"pmcid":["PMC8364191"],"funding_grant_id":["R35 GM127035"],"pubmed_authors":["Kaufman PD","Zhu LJ","Iyer DR","Garwain O","Li R","Sun X"],"additional_accession":[]},"is_claimable":false,"name":"The chromatin-binding domain of Ki-67 together with p53 protects human chromosomes from mitotic damage.","description":"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.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Aug","modification":"2025-04-04T19:17:11.333Z","creation":"2025-04-04T19:17:11.333Z"},"accession":"S-EPMC8364191","cross_references":{"pubmed":["34353903"],"doi":["10.1073/pnas.2021998118"]}}