Journal article
Plk1 protects kinetochore-centromere architecture against microtubule pulling forces
EMBO reports, Vol.20(10), pp.e48711-n/a
10/04/2019
DOI: 10.15252/embr.201948711
PMCID: PMC6776907
PMID: 31468671
Abstract
During mitosis, sister chromatids attach to microtubules which generate 700 pN pulling force focused on the centromere. We report that chromatin-localized signals generated by Polo-like kinase 1 (Plk1) maintain the integrity of the kinetochore and centromere against this force. Without sufficient Plk1 activity, chromosomes become misaligned after normal condensation and congression. These chromosomes are silent to the mitotic checkpoint, and many lag and mis-segregate in anaphase. Their centromeres and kinetochores lack CENP-A, CENP-C, CENP-T, Hec1, Nuf2, and Knl1; however, CENP-B is retained. CENP-A loss occurs coincident with secondary misalignment and anaphase onset. This disruption occurs asymmetrically prior to anaphase and requires tension generated by microtubules. Mechanistically, centromeres highly recruit PICH DNA helicase and PICH depletion restores kinetochore disruption in pre-anaphase cells. Furthermore, anaphase defects are significantly reduced by tethering Plk1 to chromatin, including H2B, and INCENP, but not to CENP-A. Taken as a whole, this demonstrates that Plk1 signals are crucial for stabilizing centromeric architecture against tension.
Details
- Title: Subtitle
- Plk1 protects kinetochore-centromere architecture against microtubule pulling forces
- Creators
- Robert F. Lera - Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Hematol Oncol, Madison, WI 53706 USARoshan X. Norman - Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Hematol Oncol, Madison, WI 53706 USAMarie Dumont - Université Paris Sciences et LettresAlexandra Dennee - Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Hematol Oncol, Madison, WI 53706 USAJoanne Martin-Koob - Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Hematol Oncol, Madison, WI 53706 USADaniele Fachinetti - Université Paris Sciences et LettresMark E. Burkard - Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Hematol Oncol, Madison, WI 53706 USA
- Resource Type
- Journal article
- Publication Details
- EMBO reports, Vol.20(10), pp.e48711-n/a
- Publisher
- Wiley
- DOI
- 10.15252/embr.201948711
- PMID
- 31468671
- PMCID
- PMC6776907
- ISSN
- 1469-221X
- eISSN
- 1469-3178
- Number of pages
- 16
- Grant note
- P30 CA014520 / University of Wisconsin Carbone Cancer Center Support Grant P30CA014520 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01 GM097245 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 10/04/2019
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984701255902771
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