Authors: | Tsou, M. F. B.; Wang, W. J.; George, K. A.; Uryu, K.; Stearns, T.; Jallepalli, P. V. |
Article Title: | Polo Kinase and Separase Regulate the Mitotic Licensing of Centriole Duplication in Human Cells |
Abstract: | It has been proposed that separase-dependent centriole disengagement at anaphase licenses centrosomes for duplication in the next cell cycle. Here we test whether such a mechanism exists in intact human cells. Loss of separase blocked centriole disengagement during mitotic exit and delayed assembly of new centrioles during the following S phase; however, most engagements were eventually dissolved. We identified Polo-like kinase 1 (Plk1) as a parallel activator of centriole disengagement. Timed inhibition of Plk1 mapped its critical period of action to late G2 or early M phase, i.e., prior to securin destruction and separase activation at anaphase onset. Crucially, when cells exited mitosis after downregulation of both separase and Plk1, centriole disengagement failed completely, and subsequent centriole duplication in interphase was also blocked. Our results indicate that Plk1 and separase act at different times during M phase to license centrosome duplication, reminiscent of their roles in removing cohesin from chromosomes. © 2009 Elsevier Inc. All rights reserved. |
Keywords: | controlled study; human cell; gene deletion; exons; proto-oncogene proteins; mitosis; cohesin; cell cycle proteins; cell cycle; cell cycle s phase; enzyme inhibition; models, biological; protein depletion; enzyme activation; enzyme activity; cell line, tumor; gene expression regulation; enzyme regulation; polo like kinase 1; protein-serine-threonine kinases; cellbio; anaphase; microscopy, fluorescence; models, genetic; cellcycle; cell cycle g2 phase; cell cycle m phase; cell nucleus; histones; cell strain hct116; securin; separase; centriole; peptide mapping; centrioles; endopeptidases |
Journal Title: | Developmental Cell |
Volume: | 17 |
Issue: | 3 |
ISSN: | 1534-5807 |
Publisher: | Cell Press |
Date Published: | 2009-09-15 |
Start Page: | 344 |
End Page: | 354 |
Language: | English |
DOI: | 10.1016/j.devcel.2009.07.015 |
PUBMED: | 19758559 |
PROVIDER: | scopus |
PMCID: | PMC2746921 |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 16" - "Export Date: 30 November 2010" - "CODEN: DCEEB" - "Source: Scopus" |