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dc.contributor.authorGarwain, Osama
dc.contributor.authorSun, Xiaoming
dc.contributor.authorRamalingam Iyer, Divya
dc.contributor.authorLi, Rui
dc.contributor.authorZhu, Lihua Julie
dc.contributor.authorKaufman, Paul D.
dc.date2022-08-11T08:08:25.000
dc.date.accessioned2022-08-23T15:54:52Z
dc.date.available2022-08-23T15:54:52Z
dc.date.issued2020-10-16
dc.date.submitted2020-12-03
dc.identifier.citation<p>bioRxiv 2020.10.16.342352; doi: https://doi.org/10.1101/2020.10.16.342352. <a href="https://doi.org/10.1101/2020.10.16.342352" target="_blank" title="preprint in bioRxiv">Link to preprint on bioRxiv.</a></p>
dc.identifier.doi10.1101/2020.10.16.342352
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29635
dc.description<p>This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.</p>
dc.description.abstractVertebrate 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.
dc.language.isoen_US
dc.relationNow published in Proceedings of the National Academy of Sciences doi: 10.1073/pnas.2021998118
dc.rightsThe copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCell Biology
dc.subjectDNA damage
dc.subjectKi-67
dc.subjectproteins
dc.subjectCell Biology
dc.subjectGenetics and Genomics
dc.titleThe chromatin-binding domain of Ki-67 together with p53 protects human chromosomes from mitotic damage [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2856&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1851
dc.identifier.contextkey20390729
refterms.dateFOA2022-08-23T15:54:53Z
html.description.abstract<p><p id="x-x-x-p-4">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.</p>
dc.identifier.submissionpathfaculty_pubs/1851
dc.contributor.departmentDepartment of Molecular, Cell and Cancer Biology


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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.