Chromosome association of minichromosome maintenance proteins in Drosophila mitotic cycles.
Minichromosome maintenance (MCM) proteins are essential DNA replication factors conserved among eukaryotes. MCMs cycle between chromatin bound and dissociated states during each cell cycle. Their absence on chromatin is thought to contribute to the inability of a G2 nucleus to replicate DNA. Passage through mitosis restores the ability of MCMs to bind chromatin and the ability to replicate DNA. In Drosophila early embryonic cell cycles, which lack a G1 phase, MCMs reassociate with condensed chromosomes toward the end of mitosis. To explore the coupling between mitosis and MCM-chromatin interaction, we tested whether this reassociation requires mitotic degradation of cyclins. Arrest of mitosis by induced expression of nondegradable forms of cyclins A and/or B showed that reassociation of MCMs to chromatin requires cyclin A destruction but not cyclin B destruction. In contrast to the earlier mitoses, mitosis 16 (M16) is followed by G1, and MCMs do not reassociate with chromatin at the end of M16. dacapo mutant embryos lack an inhibitor of cyclin E, do not enter G1 quiescence after M16, and show mitotic reassociation of MCM proteins. We propose that cyclin E, inhibited by Dacapo in M16, promotes chromosome binding of MCMs. We suggest that cyclins have both positive and negative roles in controlling MCM-chromatin association.
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Department of Biochemistry and Biophysics, University of California San Francisco 94143-0448, USA.
O'Farrell
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D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016213:Cyclins / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000235:genetics* / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D018797:Cell Cycle Proteins; D016213:Cyclins; D029721:Drosophila Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; C103336:dap protein, Drosophila