Journal
JOURNAL OF CELL BIOLOGY
Volume 165, Issue 6, Pages 789-800Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200404092
Keywords
cyclin E; MCM protein; prereplication complex assembly; DNA replicatiom; cyclin E deregulation
Categories
Funding
- NCI NIH HHS [CA78343, P01 CA013106, R01 CA078343, R56 CA078343, CA13106] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available