Journal
GENETICS
Volume 179, Issue 4, Pages 1757-1768Publisher
GENETICS SOCIETY AMERICA
DOI: 10.1534/genetics.108.088690
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Funding
- NCI NIH HHS [P30 CA046934] Funding Source: Medline
- NIGMS NIH HHS [GM-35078, R01 GM035078, GM-070403, F31 GM070403] Funding Source: Medline
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Mcm proteins are an important family of evolutionarily conserved helicases required for DNA replication in eukaryotes. The eukaryotic Mcm complex of Six paralogs that form a heterohexameric ring. Because the intact. Mcm2-7 hexamer is inactive in vitro, it has been difficult to determine the precis-c function of the different subunits. The solved atomic structure of an archaeal minichromosome maintenance (MCM) homolog provides insight into the function of eukaryotic Mcm proteins. The N-terminal positively charged Central channel in the archaeal molecule consists of beta-hairpin domains essential for DNA binding in vitro. Eukaryotic Mcm proteins also have beta-hairpin domains, but their functions is un-known. With the archaeal atomic structure as a guide, yeast molecular genetics was used to query the functions of the beta-hairpin domains in vivo. A Yeast mcm5 mutant with beta-hairpin mutations displays defects ill the G1/S transition of the cell cycle, the initiation phase of DNA replication, and in the binding of the entire Mcm2-7 complex to replication origins. A similar mcm4 mutation is synthetically lethal with the mcm5 mutation. Therefore, in addition to its known regulatory role, Mcm5 protein has a positive role in origin binding, which requires coordination by all six subunits in the hexamer.
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