Multiple roles for separase auto-cleavage during the G2/M transition Journal Article
| Authors: | Papi, M.; Berdougo, E.; Randall, C. L.; Ganguly, S.; Jallepalli, P. V. |
| Article Title: | Multiple roles for separase auto-cleavage during the G2/M transition |
| Abstract: | The cysteine protease separase triggers anaphase onset by cleaving chromosome-bound cohesin. In humans, separase also cleaves itself at multiple sites, but the biological significance of this reaction has been elusive. Here we show that preventing separase auto-cleavage, via targeted mutagenesis of the endogenous hSeparase locus in somatic cells, interferes with entry into and progression through mitosis. The initial delay in mitotic entry was not dependent on the G2 DNA damage checkpoint, but rather involved improper stabilization of the mitosis-inhibiting kinase Wee1. During M phase, cells deficient in separase auto-cleavage exhibited striking defects in spindle assembly and metaphase chromosome alignment, revealing an additional early mitotic function for separase. Both the G2 and M phase phenotypes could be recapitulated by separase RNA interference and corrected by re-expressing wild-type separase in trans. We conclude that separase auto-cleavage coordinates multiple aspects of the G2/M programme in human cells, thus contributing to the timing and efficiency of chromosome segregation. © 2005 Nature Publishing Group. |
| Keywords: | controlled study; protein expression; human cell; protein function; mitosis; phenotype; cell cycle proteins; chromosomal proteins, non-histone; dna damage; gene targeting; cell cycle; cell division; somatic cell; protein assembly; protein degradation; cell line; protein stability; gene locus; rna interference; hela cells; wild type; time factors; nuclear proteins; rna; dna; sequence alignment; protein transport; anaphase; mitosis spindle; cell cycle g2 phase; chromosomes, human; phosphotransferase; mutagenesis; metaphase; chromosome segregation; g2 phase; separase; endopeptidases; fungal proteins; phase transition; mitosis inhibition; metaphase chromosome |
| Journal Title: | Nature Cell Biology |
| Volume: | 7 |
| Issue: | 10 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2005-10-01 |
| Start Page: | 1029 |
| End Page: | 1035 |
| Language: | English |
| DOI: | 10.1038/ncb1303 |
| PUBMED: | 16138084 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 35" - "Export Date: 24 October 2012" - "CODEN: NCBIF" - "Source: Scopus" |
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4Berdougo -
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Randall -
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Ganguly
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