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DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1
Author(s) -
Ralph Emma,
Boye Erik,
Kearsey Stephen E
Publication year - 2006
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400827
Subject(s) - ddb1 , dna replication factor cdt1 , dna damage , biology , genome instability , dna re replication , schizosaccharomyces pombe , microbiology and biotechnology , dna replication , licensing factor , ubiquitin ligase , g2 m dna damage checkpoint , dna repair , origin recognition complex , ubiquitin , replication factor c , schizosaccharomyces , eukaryotic dna replication , genetics , dna , cell cycle , cell cycle checkpoint , saccharomyces cerevisiae , yeast , gene
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.