Mcm3 is polyubiquitinated during mitosis before establishment of the pre-replication complex.
To ensure fidelity in genome duplication, eukaryotes restrict DNA synthesis to once every cell division by a cascade of regulated steps. Central to this cascade is the periodic assembly of the hexameric MCM2-7 complex at replication origins. However, in Saccharomyces cerevisiae, only a fraction of each MCM protein is able to assemble into hexamers and associate with replication origins during M phase, suggesting that MCM complex assembly and recruitment may be regulated post-translationally. Here we show that a small fraction of Mcm3p is polyubiquitinated at the onset of MCM complex assembly. Reducing the rate of ubiquitination by uba1-165, a suppressor of mcm3-10, restored the interaction of Mcm3-10p with subunits of the MCM complex and its recruitment to the replication origin. Possible roles for ubiquitinated Mcm3p in the assembly of the MCM complex at replication origins are discussed.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853-2703, USA.
Irene H
IH
Cheng
Louis A
LA
Roberts
Bik K
BK
Tye
D018797:Cell Cycle Proteins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000502:physiology; D004261:DNA Replication; D008025:Ligases / Q000502:physiology; D008938:Mitosis / Q000502:physiology*; D009097:Multienzyme Complexes / Q000502:physiology; D046988:Proteasome Endopeptidase Complex; D012441:Saccharomyces cerevisiae; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases
D018797:Cell Cycle Proteins; D009097:Multienzyme Complexes; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases