Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template

Ubiquitous environmental and endogenous genotoxic agents cause DNA lesions that can interfere with normal DNA metabolism including DNA replication, eventually resulting in mutations that lead to carcinogenesis and/or cell death. Cells possess repair mechanisms like nucleotide excision and base excision repair pathways to maintain the integrity of the genome. However, some types of lesions are repaired very inefficiently and others may not be recognized and repaired before the lesion-containing DNA undergoes DNA replication. To prevent acute cell death through arrested DNA replication at unrepaired lesions, cells have a mechanism, referred to as translesion synthesis (TLS), which allows DNA synthesis to proceed past lesions. TLS depends on the Y family of DNA polymerases (Lindahl and Wood 1999, Masutani et al. 2000, Yang 2014).

普遍存在的环境及内源致突变剂引发DNA损伤，这些损伤可能干扰正常的DNA代谢过程，包括DNA复制，最终导致突变，引发癌变或细胞死亡。细胞具备如核苷酸切除和碱基切除修复途径等修复机制，以维持基因组完整性。然而，某些类型的损伤修复效率极低，而另一些损伤可能在含有损伤DNA进行DNA复制之前，未能被识别和修复。为防止因未修复损伤处的DNA复制停滞导致的急性细胞死亡，细胞拥有一套被称为跨损伤合成（TLS）的机制，该机制允许DNA合成在损伤处继续进行。跨损伤合成依赖于Y家族DNA聚合酶（Lindahl和Wood 1999，Masutani等2000，Yang 2014）。