Crosstalk of translesion synthesis and checkpoint mechanisms

人类Polh是色素干皮变异体的负责基因产物，这是一种易患癌症的综合征。Polh催化翻译DNA合成（TLS）非常有效地通过了最突出的紫外线诱导的DNA损伤环丁烷嘧啶二聚体（CPD）。另一方面，Polh无法绕过另一种紫外线诱导的DNA损伤，即6-4光产物，导致细胞周期检查点机制的激活。本项目旨在解决TLS和细胞周期检查点机制之间的关系。Polh或PCNA突变体的表达影响细胞周期检查点，提示TLS与人类细胞中的检查点机制存在联系。

Human Polh is the responsible gene product of xeroderma pigmentosum variant, a cancer prone syndrome. Polh catalyzes translesion DNA synthesis (TLS) past the most prominent UV-induced DNA lesion, cyclobutane pyrimidine dimer (CPD), very efficiently. On the other hand, Polh is unable to bypass another UV-induced DNA lesion, 6-4 photoproduct, resulting in the activation of cell cycle checkpoint mechanisms. This project aimes to address the relations between TLS and cell cycle checkpoint mechanisms. Expression of Polh or PCNA mutants affected cell cycle checkpoint, suggesting a linkage of TLS and checkpoint mechanisms in human cells.