Deregulation of cyclin E in human cells interferes with prereplication complex assembly

Ekholm-Reed, S., Mendez, J., Tedesco, D., Zetterberg, A., Stillman, B., Reed, S. I. (June 2004) Deregulation of cyclin E in human cells interferes with prereplication complex assembly. Journal of Cell Biology, 165 (6). pp. 789-800. ISSN 0021-9525

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DOI: 10.1083/jcb.200404092


Deregulation of cyclin E expression has been associated with a broad spectrum of human malignancies. Analysis of DNA replication in cells constitutively expressing cyclin E at levels similar to those observed in a subset of tumor-derived cell lines indicates that initiation of replication and possibly fork movement are severely impaired. Such cells show a specific defect in loading of initiator proteins Mcm4, Mcm7, and to a lesser degree, Mcm2 onto chromatin during telophase and early G1 when Mcm2-7 are normally recruited to license origins of replication. Because minichromosome maintenance complex proteins are thought to function as a heterohexamer, loading of Mcm2-, Mcm4-, and Mcm7-depleted complexes is likely to underlie the S phase defects observed in cyclin E-deregulated cells, consistent with a role for minichromosome maintenance complex proteins in initiation of replication and fork movement. Cyclin E-mediated impairment of DNA replication provides a potential mechanism for chromosome instability observed as a consequence of cyclin E deregulation.

Item Type: Paper
Uncontrolled Keywords: cyclin E MCM protein prereplication complex assembly DNA replicatiom cyclin E deregulation ORIGIN RECOGNITION COMPLEX origin recognition complex MINICHROMOSOME MAINTENANCE PROTEINS minichromosome maintenance proteins NUCLEAR ANTIGEN PCNA nuclear antigen DNA-REPLICATION DNA replication S-PHASE S-Phase BREAST-CANCER breast cancer SACCHAROMYCES-CEREVISIAE Saccharomyces Cerevisiae PROGNOSTIC IMPLICATIONS prognostic implications CHROMOSOME chromosome INSTABILITY instability GENOMIC INSTABILITY
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
diseases & disorders > cancer > cancer types > breast cancer
CSHL Authors:
Communities: CSHL labs > Stillman lab
Highlight: Stillman, Bruce W.
Depositing User: CSHL Librarian
Date: June 2004
Date Deposited: 03 Feb 2012 16:19
Last Modified: 20 Jun 2017 18:16
PMCID: PMC2172392
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