Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China.
Biomolecules. 2021 Oct 19;11(10):1543. doi: 10.3390/biom11101543.
DNA lesions escaping from repair often block the DNA replicative polymerases required for DNA replication and are handled during the S/G2 phases by the DNA damage tolerance (DDT) mechanisms, which include the error-prone translesion synthesis (TLS) and the error-free template switching (TS) pathways. Where the mono-ubiquitylation of PCNA K164 is critical for TLS, the poly-ubiquitylation of the same residue is obligatory for TS. However, it is not known how cells divide the labor between TLS and TS. Due to the fact that the type of DNA lesion significantly influences the TLS and TS choice, we propose that, instead of altering the ratio between the mono- and poly-Ub forms of PCNA, the competition between TLS and TS would automatically determine the selection between the two pathways. Future studies, especially the single integrated lesion "i-Damage" system, would elucidate detailed mechanisms governing the choices of specific DDT pathways.
DNA 损伤如果未能被修复，往往会阻断 DNA 复制所需的聚合酶，在 S/G2 期，这些损伤会被 DNA 损伤容忍（DDT）机制处理，包括易错的跨损伤合成（TLS）和无差错模板转换（TS）途径。PCNA K164 的单泛素化对 TLS 至关重要，而同一残基的多泛素化则是 TS 的必要条件。然而，目前尚不清楚细胞如何在 TLS 和 TS 之间分配工作。由于 DNA 损伤的类型会显著影响 TLS 和 TS 的选择，我们提出，不是改变 PCNA 的单泛素和多泛素形式之间的比例，而是 TLS 和 TS 之间的竞争会自动决定两条途径的选择。未来的研究，特别是单整合损伤“i-Damage”系统，将阐明控制特定 DDT 途径选择的详细机制。
