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PMID: 12381663 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Deregulated G1-cyclin expression induces genomic instability by preventing efficient pre-RC formation.

Genes & development ·Vol. 16 ·No. 20 ·2002-10-15 ·Pages 2639-49

Tanaka S, Diffley JF

Abstract

Although genomic instability is a hallmark of human cancer cells, the mechanisms by which genomic instability is generated and selected for during oncogenesis remain obscure. In most human cancers, the pathway leading to the activation of the G1 cyclins is deregulated. Using budding yeast as a model, we show that overexpression of the G1 cyclin Cln2 inhibits the assembly of prereplicative complexes (pre-RCs) and induces gross chromosome rearrangements (GCR). Our results suggest that deregulation of G1 cyclins, selected for in oncogenesis because it confers clonal growth advantage, may also provide an important mechanism for generating genomic instability by inhibiting replication licensing.

MeSH Terms
Cell Cycle/physiology Chromosomal Proteins, Non-Histone Chromosome Aberrations Chromosomes, Fungal Cyclin B/genetics,metabolism Cyclin G Cyclin G1 Cyclin-Dependent Kinase Inhibitor Proteins Cyclins/genetics,metabolism DNA Footprinting DNA Replication/physiology Enzyme Inhibitors/pharmacology Fungal Proteins/metabolism,pharmacology Humans Immunoblotting Nucleic Acid Hybridization Plasmids Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins Tripeptidyl-Peptidase 1
Chemicals
CCNG1 protein, human CLN2 protein, S cerevisiae Chromosomal Proteins, Non-Histone Cyclin B Cyclin G Cyclin G1 Cyclin-Dependent Kinase Inhibitor Proteins Cyclins Enzyme Inhibitors Fungal Proteins SIC1 protein, S cerevisiae Saccharomyces cerevisiae Proteins Tripeptidyl-Peptidase 1 TPP1 protein, human MCM2 protein, S cerevisiae
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Tanaka Seiji
Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
Diffley John F X
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1011002
Published
2002-10-15
Pages
2639-49
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC187461
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.1011002 PMC Full Text View journal details
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