Mcm7, a subunit of the presumptive MCM helicase, modulates its own expression in conjunction with Mcm1.
The Saccharomyces cerevisiae Mcm7 protein is a subunit of the presumed heteromeric MCM helicase that melts origin DNA and unwinds replication forks. Previous work showed that Mcm1 binds constitutively to the MCM7 promoter and regulates MCM7 expression. Here, we identify Mcm7 as a novel cofactor of Mcm1 in the regulation of MCM7 expression. Transcription of MCM7 is increased in the mcm7-1 mutant and decreased in the mcm1-1 mutant, suggesting that Mcm7 modulates its own expression in conjunction with Mcm1. Indeed, Mcm7 stimulates Mcm1 binding to the early cell cycle box upstream of the promoters of MCM7 as well as CDC6 and MCM5. Whereas Mcm1 binds these promoters constitutively, Mcm7 is recruited during late M phase, consistent with Mcm7 playing a direct role in modulating the periodic expression of early cell cycle genes. The multiple roles of Mcm7 in replication initiation, replication elongation, and autoregulation parallel those of the oncoprotein, the large T-antigen of the SV40 virus.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853-2703, USA.
Michael J
MJ
Fitch
Justin J
JJ
Donato
Bik K
BK
Tye
D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005557:Formaldehyde / Q000494:pharmacology; D026341:Minichromosome Maintenance 1 Protein / Q000235:genetics / Q000378:metabolism*; D064168:Minichromosome Maintenance Complex Component 7; D008938:Mitosis; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013696:Temperature
D000952:Antigens, Polyomavirus Transforming; C066503:CDC6 protein, S cerevisiae; D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D026341:Minichromosome Maintenance 1 Protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D005557:Formaldehyde; D012313:RNA; D003850:Deoxyribonuclease I; C491088:MCM7 protein, S cerevisiae; D064168:Minichromosome Maintenance Complex Component 7