DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1.
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.
Ralph
Emma
E
Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.
Boye
Erik
E
Kearsey
Stephen E
SE
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology / Q000528:radiation effects; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology* / Q000528:radiation effects; D006868:Hydrolysis; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C506543:Cdt2 protein, S pombe; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C500125:Ddb1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C406818:cdt1 protein, S pombe; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C456840:rad3 protein, S pombe