Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells

Yan, Z., DeGregori, J., Shohet, R., Leone, G., Stillman, B., Nevins, J. R., Williams, R. S. (1998) Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells. Proceedings of the National Academy of Sciences of the United States of America, 95 (7). pp. 3603-3608. ISSN 0027-8424

URL: http://www.ncbi.nlm.nih.gov/pubmed/9520412
DOI: 10.1073/pnas.95.7.3603

Abstract

Cdc6 has a critical regulatory role in the initiation of DNA replication in yeasts, but its function in mammalian cells has not been characterized. We show here that Cdc6 is expressed selectively in proliferating but not quiescent mammalian cells, both in culture and within tissues of intact animals. During the transition from a growth-arrested to a proliferative state, transcription of mammalian Cdc6 is regulated by E2F proteins, as revealed by a functional analysis of the human Cdc6 promoter and by the ability of exogenously expressed E2F proteins to stimulate the endogenous Cdc6 gene. Immunodepletion of Cdc6 by microinjection of anti-Cdc6 antibody blocks initiation of DNA replication in a human tumor cell line. We conclude that expression of human Cdc6 is regulated in response to mitogenic signals though transcriptional control mechanisms involving E2F proteins, and that Cdc6 is required for initiation of DNA replication in mammalian cells.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
bioinformatics > genomics and proteomics > annotation > gene expression profiling annotation
CSHL Authors:
Communities: CSHL labs > Stillman lab
Highlight: Stillman, Bruce W.
Depositing User: CSHL Librarian
Date Deposited: 17 Feb 2012 19:58
Last Modified: 20 Jun 2017 19:29
PMCID: PMC19882
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25145

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