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PMID: 17039252 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1.

EMBO reports ·Vol. 7 ·No. 11 ·2006-11-00 ·Pages 1134-9

Ralph E, Boye E, Kearsey SE

Abstract

Cdt1 is an essential protein required for licensing of replication origins. Here, we show that in Schizosaccharomyces pombe, Cdt1 is proteolysed in M and G1 phases in response to DNA damage and that this mechanism seems to be conserved from yeast to Metazoa. This degradation does not require Rad3 and Cds1, indicating that it is independent of classic DNA damage and replication checkpoint pathways. Damage-induced degradation of Cdt1 is dependent on Cdt2 and Ddb1, which are components of a Cul4 ubiquitin ligase. We also show that Cdt2 and Ddb1 are needed for cell-cycle changes in Cdt1 levels in the absence of DNA damage. Cdt2 and Ddb1 have been shown to be involved in the degradation of the Spd1 inhibitor of ribonucleotide reductase after DNA damage, and we speculate that Cdt1 downregulation might contribute to genome stability by reducing demand on dNTP pools during DNA repair.

MeSH Terms
Adaptor Proteins, Signal Transducing/genetics,physiology Cell Cycle Cell Cycle Proteins/genetics,metabolism,physiology,radiation effects Checkpoint Kinase 2 DNA Damage DNA-Binding Proteins/genetics,metabolism,physiology,radiation effects Hydrolysis Protein Kinases/genetics,physiology Schizosaccharomyces/metabolism Schizosaccharomyces pombe Proteins/genetics,metabolism,physiology,radiation effects Signal Transduction
Chemicals
Adaptor Proteins, Signal Transducing Cdt2 protein, S pombe Cell Cycle Proteins DNA-Binding Proteins Ddb1 protein, S pombe Schizosaccharomyces pombe Proteins cdt1 protein, S pombe Protein Kinases Checkpoint Kinase 2 rad3 protein, S pombe
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ralph Emma
Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.
Boye Erik
Kearsey Stephen E
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36 references, click to expand
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Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-221X
DOI
10.1038/sj.embor.7400827
Published
2006-11-00
Epub
2006-00-13
Pages
1134-9
Language
English
Region
England
NLM ID
100963049
PMCID
PMC1679788
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1038/sj.embor.7400827 PMC Full Text View journal details
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