Post-Translational Modifications of PCNA in Control of DNA Synthesis and DNA Damage Tolerance-the Implications in Carcinogenesis

作者：Siyi Zhang, Tingting Zhou, Zhuo Wang, Fei Yi, Chunlu Li, Wendong Guo, Hongde Xu, Hongyan Cui, Xiang Da Dong, Jingwei Liu, Xiaoyu Song, Liu Cao · 发表于：International Journal of Biological Sciences · 年份：2021 · DOI：10.7150/ijbs.64628 · 被引用次数：52 · 研究领域：DNA Repair Mechanisms、Microtubule and mitosis dynamics、Genomics and Chromatin Dynamics

The faithful DNA replication is a critical event for cell survival and inheritance. However, exogenous or endogenous sources of damage challenge the accurate synthesis of DNA, which causes DNA lesions. The DNA lesions are obstacles for replication fork progression. However, the prolonged replication fork stalling leads to replication fork collapse, which may cause DNA double-strand breaks (DSB). In order to maintain genomic stability, eukaryotic cells evolve translesion synthesis (TLS) and template switching (TS) to resolve the replication stalling. Proliferating cell nuclear antigen (PCNA) trimer acts as a slide clamp and encircles DNA to orchestrate DNA synthesis and DNA damage tolerance (DDT). The post-translational modifications (PTMs) of PCNA regulate these functions to ensure the appropriate initiation and termination of replication and DDT. The aberrant regulation of PCNA PTMs will result in DSB, which causes mutagenesis and poor response to chemotherapy. Here, we review the roles of the PCNA PTMs in DNA duplication and DDT. We propose that clarifying the regulation of PCNA PTMs may provide insights into understanding the development of cancers.