Negative regulation of geminin by CDK-dependent ubiquitination controls replication licensing.
The replication licensing system ensures the precise duplication of chromosomal DNA in each cell cycle. In metazoans, a small protein called geminin plays a central role in negatively regulating licensing late in the cell cycle. Recent work using Xenopus egg extracts shows how geminin activity is downregulated on exit from metaphase in a process that requires mitotic cyclin-dependent kinases (CDKs). Geminin is polyubiquitinated by the Anaphase Promoting Complex, but instead of being proteolysed-the normal fate of polyubiquitinated proteins-much of the geminin is deubiquitinated, leaving it inactive. These results suggest a simple model for how precise chromosome duplication is ensured in the Xenopus model system.
Li
Anatoliy
A
Wellcome Trust Biocentre, University of Dundee, Dundee, Scotland, UK.
Blow
J Julian
JJ
D000705:Anaphase; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D016193:G1 Phase; D064248:Geminin; D005786:Gene Expression Regulation; D008677:Metaphase; D008938:Mitosis; D008954:Models, Biological; D016196:S Phase; D025801:Ubiquitin / Q000378:metabolism; D014981:Xenopus; D029867:Xenopus Proteins
D018797:Cell Cycle Proteins; C577998:GMNN protein, Xenopus; D064248:Geminin; D025801:Ubiquitin; D029867:Xenopus Proteins; D004247:DNA; D018844:Cyclin-Dependent Kinases