DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1
DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1
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DOI：
10.1038/sj.embor.7400827
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发表时间：
2006-11-01
期刊：
影响因子：
7.7
通讯作者：
Kearsey, Stephen E.
中科院分区：
文献类型：
--
作者：
Ralph, Emma;Boye, Erik;Kearsey, Stephen E.
Cdt1 是复制起点许可所需的必需蛋白质。在这里，我们表明，在粟酒裂殖酵母中，Cdt1 在 M 期和 G1 期响应 DNA 损伤而被蛋白水解，并且这种机制似乎从酵母到后生动物都是保守的。这种降解不需要 Rad3 和 Cds1，表明它独立于经典的 DNA 损伤和复制检查点途径。损伤诱导的 Cdt1 降解依赖于 Cdt2 和 Ddb1，它们是 Cul4 泛素连接酶的组成部分。我们还表明，在没有 DNA 损伤的情况下，Cdt2 和 Ddb1 是细胞周期中 Cdt1 水平变化所必需的。 Cdt2 和 Ddb1 已被证明参与 DNA 损伤后核糖核苷酸还原酶 Spd1 抑制剂的降解，我们推测 Cdt1 下调可能通过减少 DNA 修复过程中对 dNTP 库的需求来促进基因组稳定性。
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.