Non-proteolytic inactivation of geminin requires CDK-dependent ubiquitination

Anatoliy Li; J. Julian Blow

doi:10.1038/ncb1100

Non-proteolytic inactivation of geminin requires CDK-dependent ubiquitination

Anatoliy Li
, J. Julian Blow

Research output: Contribution to journal › Article › peer-review

67 Citations (Scopus)

Abstract

In late mitosis and G1, a complex of the essential initiation proteins Mcm2–7 are assembled onto replication origins to 'license' them for initiation. At other times licensing is inhibited by cyclin-dependent kinases (CDKs) and geminin, thus ensuring that origins fire only once per cell cycle. Here we show that, paradoxically, CDKs are also required to inactivate geminin and activate the licensing system. On exit from metaphase in Xenopus laevis egg extracts, CDK-dependent activation of the anaphase-promoting complex (APC/C) results in the transient polyubiquitination of geminin. This ubiquitination triggers geminin inactivation without requiring ubiquitin-dependent proteolysis, and is essential for replication origins to become licensed. This reveals an unexpected role for CDKs and ubiquitination in activating chromosomal DNAreplication.

Original language	English
Pages (from-to)	260-267
Number of pages	8
Journal	Nature Cell Biology
Volume	6
Issue number	3
DOIs	https://doi.org/10.1038/ncb1100
Publication status	Published - Mar 2004

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abstract = "In late mitosis and G1, a complex of the essential initiation proteins Mcm2{\textendash}7 are assembled onto replication origins to 'license' them for initiation. At other times licensing is inhibited by cyclin-dependent kinases (CDKs) and geminin, thus ensuring that origins fire only once per cell cycle. Here we show that, paradoxically, CDKs are also required to inactivate geminin and activate the licensing system. On exit from metaphase in Xenopus laevis egg extracts, CDK-dependent activation of the anaphase-promoting complex (APC/C) results in the transient polyubiquitination of geminin. This ubiquitination triggers geminin inactivation without requiring ubiquitin-dependent proteolysis, and is essential for replication origins to become licensed. This reveals an unexpected role for CDKs and ubiquitination in activating chromosomal DNAreplication.",

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Non-proteolytic inactivation of geminin requires CDK-dependent ubiquitination

Abstract

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