Checkpoint activation regulates mutagenic translesion synthesis
Checkpoint activation regulates mutagenic translesion synthesis
复制标题
DOI：
10.1101/gad.1043203
复制
发表时间：
2003-01-01
影响因子：
10.5
通讯作者：
Wang, TSF
中科院分区：
文献类型：
--
作者：
Kai, M;Wang, TSF
细胞已经进化出检查点反应，以阻止或延迟细胞周期，激活DNA修复网络，或在基因组扰动后诱导凋亡。细胞还进化了跨损伤合成过程，以通过无错误或易错修复来耐受基因组损伤。在这里，我们表明，复制扰动后，细胞表现出一个突变表型，这可以显着影响突变的检查点元件Cds1和Rad17或translesion合成聚合酶DinB和Polzeta。细胞通过以检查点激活依赖性方式上调DinB来响应基因组扰动。此外，协会DinB与染色质是依赖于功能Rad17，DinB物理相互作用的检查点钳组件Hus1和Rad1。因此，跨损伤合成是检查点反应的一部分。
Cells have evolved checkpoint responses to arrest or delay the cell cycle, activate DNA repair networks, or induce apoptosis after genomic perturbation. Cells have also evolved the translesion synthesis processes to tolerate genomic lesions by either error-free or error-prone repair. Here, we show that after a replication perturbation, cells exhibit a mutator phenotype, which can be significantly affected by mutations in the checkpoint elements Cds1 and Rad17 or translesion synthesis polymerases DinB and Polzeta. Cells respond to genomic perturbation by up-regulation of DinB in a checkpoint activation-dependent manner. Moreover, association of DinB with chromatin is dependent on functional Rad17, and DinB physically interacts with the checkpoint-clamp components Hus1 and Rad1. Thus, translesion synthesis is a part of the checkpoint response.