| Cdc6 determines utilization of p21(WAF1/CIP1)-dependent damage checkpoint in S phase cells. | |
MedLine Citation:
|
PMID: 18458079 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
When cells traversing G(1) are irradiated with UV light, two parallel damage checkpoint pathways are activated: Chk1-Cdc25A and p53-p21(WAF1/CIP1), both targeting Cdk2, but the latter inducing a long lasting arrest. In similarly treated S phase-progressing cells, however, only the Cdc25A-dependent checkpoint is active. We have recently found that the p21-dependent checkpoint can be activated and induce a prolonged arrest if S phase cells are damaged with a base-modifying agent, such as methyl methanesulfonate (MMS) and cisplatin. But the mechanistic basis for the differential activation of the p21-dependent checkpoint by different DNA damaging agents is not understood. Here we report that treatment of S phase cells with MMS but not a comparable dose of UV light elicits proteasome-mediated degradation of Cdc6, the assembler of pre-replicative complexes, which allows induced p21 to bind Cdk2, thereby extending inactivation of Cdk2 and S phase arrest. Consistently, enforced expression of Cdc6 largely eliminates the prolonged S phase arrest and Cdk2 inactivation induced with MMS, whereas RNA interference-mediated Cdc6 knockdown not only prolongs such arrest and inactivation but also effectively activates the p21-dependent checkpoint in the UV-irradiated S phase cells. |
Authors:
|
Qiuming Kan; Shigeki Jinno; Kohei Kobayashi; Hanako Yamamoto; Hiroto Okayama |
Related Documents
:
|
3150939 - Zonal turnover of cell poles of bacillus subtilis. 9389439 - From flow cytometric brdurd data to cell population growth and doubling time. 22348179 - Magnetic nanoparticles to enhance cell seeding and distribution in tissue engineering s... 383299 - A new method for the estimation of cell cycle phases. 20406859 - Characterization of n-acetyltransferase 1 activity in human keratinocytes and modulatio... 19545789 - S-phase cells are more sensitive to high-linear energy transfer radiation. 17495519 - Signal-dependent control of autophagy and cell death in colorectal cancer cell: the rol... 11896679 - Pesticide roundup provokes cell division dysfunction at the level of cdk1/cyclin b acti... 297469 - Nature of transformation of hydrocortisone by cells incorporated into polyacrylamide gel. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-05-05 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 283 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2008 Jun |
Date Detail:
|
Created Date: 2008-06-23 Completed Date: 2008-08-18 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 17864-72 Citation Subset: IM |
Affiliation:
|
Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, University of Tokyo, Tokyo, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cell Cycle Proteins / metabolism, physiology* Cisplatin / pharmacology Cyclin-Dependent Kinase Inhibitor p21 / metabolism* DNA Damage Humans Methyl Methanesulfonate / pharmacology Mice Models, Biological Nuclear Proteins / metabolism, physiology* RNA Interference S Phase* Ultraviolet Rays cdc25 Phosphatases / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/CDC6 protein, human; 0/CDC6 protein, mouse; 0/CDKN1A protein, human; 0/Cdkn1a protein, mouse; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Nuclear Proteins; 15663-27-1/Cisplatin; 66-27-3/Methyl Methanesulfonate; EC 3.1.3.16/Cdc25a protein, mouse; EC 3.1.3.48/cdc25 Phosphatases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Tip60 is regulated by circadian transcription factor clock and is involved in cisplatin resistance.
Next Document: Genomic matrix attachment region and chromosome conformation capture quantitative real time PCR assa...