Minesinger Brenda K, Abdulovic Amy L, Ou Tingwei M, Jinks-Robertson Sue
Biochemistry, Cell and Developmental Biology Program of the Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322, USA.
DNA Repair (Amst). 2006 Feb 3;5(2):226-34. doi: 10.1016/j.dnarep.2005.10.002. Epub 2005 Nov 11.
DNA lesions can stall or block high-fidelity polymerases, thus inhibiting replication. To bypass such lesions, low-fidelity translesion synthesis (TLS) polymerases can be used to insert a nucleotide across from the lesion or extend from a lesion:base mispair. When DNA repair is compromised in Saccharomyces cerevisiae, spontaneous DNA lesions can lead to a novel mutational event in which a frameshift is accompanied by one or more base pair substitutions. These "complex frameshifts" are dependent upon the TLS polymerase Pol zeta, and provide a mutational signature for mutagenic Pol zeta-dependent activity. In the current study, we have found that a specific subset of the Pol zeta-dependent mutational events requires oxidative metabolism. These results suggest that translesion bypass of spontaneously oxidized DNA bases can be a significant source of mutagenesis in repair compromised cells.
DNA损伤会使高保真聚合酶停滞或受阻，从而抑制复制。为绕过此类损伤，可使用低保真的跨损伤合成（TLS）聚合酶在损伤对面插入一个核苷酸或从损伤：碱基错配处延伸。当酿酒酵母中的DNA修复受损时，自发的DNA损伤会导致一种新的突变事件，即移码伴随着一个或多个碱基对替换。这些“复杂移码”依赖于TLS聚合酶Pol ζ，并为诱变的Pol ζ依赖性活性提供了一种突变特征。在当前研究中，我们发现Pol ζ依赖性突变事件的一个特定子集需要氧化代谢。这些结果表明，自发氧化的DNA碱基的跨损伤绕过可能是修复受损细胞中诱变的一个重要来源。
