Abstract:
:Initiation of DNA replication requires the function of MCM gene products, which participate in ensuring that DNA replication occurs only once in the cell cycle. Expression of all mammalian genes of the MCM family is induced by growth stimulation, unlike yeast, and the mRNA levels peak at G1/S boundary. In this study, we examined the transcriptional activities of isolated human MCM gene promoters. Human MCM5 and MCM6 promoters with mutation in the E2F sites failed in promoter regulation following serum stimulation and exogenous E2F expression. In addition, we identified a novel E2F-like sequence in human MCM6 promoter which cooperates with the authentic E2F sites in E2F-dependent regulation. Forced expression of E2F1 could induce expression of all members of the endogenous MCM genes in rat embryonal fibroblast REF52 cells. Our results demonstrated that the growth-regulated expression of mammalian MCM5 and MCM6 genes, and presumably other MCM members, is primarily regulated by E2F through binding to multiple E2F sites in the promoters.
journal_name
Oncogenejournal_title
Oncogeneauthors
Ohtani K,Iwanaga R,Nakamura M,Ikeda M,Yabuta N,Tsuruga H,Nojima Hdoi
10.1038/sj.onc.1202544subject
Has Abstractpub_date
1999-04-08 00:00:00pages
2299-309issue
14eissn
0950-9232issn
1476-5594journal_volume
18pub_type
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