Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA.
Genes Dev. 2010 Jan 15;24(2):123-8. doi: 10.1101/gad.1872810.
The ultraviolet (UV)-induced (6-4) pyrimidine-pyrimidone photoproduct [(6-4) PP] confers a large structural distortion in DNA. Here we examine in human cells the roles of translesion synthesis (TLS) DNA polymerases (Pols) in promoting replication through a (6-4) TT photoproduct carried on a duplex plasmid where bidirectional replication initiates from an origin of replication. We show that TLS contributes to a large fraction of lesion bypass and that it is mostly error-free. We find that, whereas Pol eta and Pol iota provide alternate pathways for mutagenic TLS, surprisingly, Pol zeta functions independently of these Pols and in a predominantly error-free manner. We verify and extend these observations in mouse cells and conclude that, in human cells, TLS during replication can be markedly error-free even opposite a highly distorting DNA lesion.
紫外线（UV）诱导的（6-4）嘧啶-嘧啶酮光产物[(6-4)PP]在 DNA 中赋予了很大的结构扭曲。在这里，我们在人类细胞中检查了跨损伤合成（TLS）DNA 聚合酶（Pols）在通过带有双链质粒的（6-4）TT 光产物进行复制方面的作用，其中双向复制从复制起点开始。我们表明，TLS 有助于很大一部分损伤绕过，并且它主要是无错误的。我们发现，虽然 Pol eta 和 Pol iota 为诱变 TLS 提供了替代途径，但令人惊讶的是，Pol zeta 独立于这些 Pol 并以主要无错误的方式起作用。我们在小鼠细胞中验证并扩展了这些观察结果，并得出结论，在人类细胞中，即使在面对高度扭曲的 DNA 损伤时，复制过程中的 TLS 也可以明显无错误。
