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Vol. 18, Issue 4, 1447-1456, April 2007

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Nascent Transcription of MCM2-7 Is Important for Nuclear Localization of the Minichromosome Maintenance Complex in G₁

Fred Hutchinson Cancer Research Center, Basic Sciences Division, Seattle, WA 98109

Submitted September 7, 2006; Revised January 24, 2007; Accepted February 1, 2007
Monitoring Editor: Mark Solomon

The minichromosome maintenance genes (MCM2-7) are transcribed at M/G₁ just as the Mcm complex is imported into the nucleus to be assembled into prereplication complexes, during a period of low cyclin-dependent kinase (CDK) activity. The CDKs trigger DNA replication and prevent rereplication in part by exporting Mcm2-7 from the nucleus during S phase. We have found that repression of MCM2-7 transcription in a single cell cycle interferes with the nuclear import of Mcms in the subsequent M/G₁ phase. This suggests that nascent Mcm proteins are preferentially imported into the nucleus. Consistent with this, we find that loss of CDK activity in G₂/M is not sufficient for nuclear import, there is also a requirement for new protein synthesis. This requirement is not met by constitutive production of Cdc6 and does not involve synthesis of new transport machinery. The Mcm proteins generated in the previous cell cycle, which are unable to reaccumulate in the nucleus, are predominantly turned over by ubiquitin-mediated proteolysis in late mitosis/early G₁. Therefore, the nuclear localization of Mcm2-7 is dependent on nascent transcription and translation of Mcm2-7 and the elimination of CDK activity which occurs simultaneously as cells enter G₁.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Linda L. Breeden (lbreeden{at}fhcrc.org)

Abbreviations used: CDK, cyclin-dependent kinase; ECB, early cell cycle box; Mcm, minichromosome maintenance protein; ORC, origin recognition complex; pre-RC, prereplication complex.

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