Regulation of genome integrity through a DNA replication coupled feedback control

为了确保DNA复制在细胞周期中被限制为只有一次，一旦DNA复制开始，启动蛋白CDT1就会被降解。我们研究了依赖于增殖细胞核抗原的CRL4-CDT2是如何作用于CDT1的降解的。我们报道了CRL4-CDT2识别位于CDT1 N端的特定残基，并且在S期和修复过程中不同地需要增殖细胞核抗原加载物。CDT1的降解受到严格的调控，以保持基因组的完整性。

To ensure that DNA replication is limited to only once during a cell cycle, initiator protein Cdt1 is degraded once DNA replication is initiated. We examined how PCNA dependent CRL4-Cdt2 operates for the degradation of Cdt1.We report that CRL4-Cdt2 recognizes specific residues located at the N-terminus of Cdt1 and that PCNA loaders are differentially required during S phase and repair. Cdt1 degradation is strictly regulated to maintain genome integrity.