Godoy Veronica G, Jarosz Daniel F, Simon Sharotka M, Abyzov Alexej, Ilyin Valentin, Walker Graham C
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mol Cell. 2007 Dec 28;28(6):1058-70. doi: 10.1016/j.molcel.2007.10.025.
DinB is the only translesion Y family DNA polymerase conserved among bacteria, archaea, and eukaryotes. DinB and its orthologs possess a specialized lesion bypass function but also display potentially deleterious -1 frameshift mutagenic phenotypes when overproduced. We show that the DNA damage-inducible proteins UmuD(2) and RecA act in concert to modulate this mutagenic activity. Structural modeling suggests that the relatively open active site of DinB is enclosed by interaction with these proteins, thereby preventing the template bulging responsible for -1 frameshift mutagenesis. Intriguingly, residues that define the UmuD(2)-interacting surface on DinB statistically covary throughout evolution, suggesting a driving force for the maintenance of a regulatory protein-protein interaction at this site. Together, these observations indicate that proteins like RecA and UmuD(2) may be responsible for managing the mutagenic potential of DinB orthologs throughout evolution.
DinB是细菌、古细菌和真核生物中唯一保守的跨损伤Y家族DNA聚合酶。DinB及其直系同源物具有特殊的损伤旁路功能，但过量表达时也会表现出潜在有害的 -1 移码诱变表型。我们发现，DNA损伤诱导蛋白UmuD(2)和RecA协同作用来调节这种诱变活性。结构建模表明，DinB相对开放的活性位点通过与这些蛋白质的相互作用而被封闭，从而防止了导致 -1 移码诱变的模板凸起。有趣的是，在整个进化过程中，定义DinB上与UmuD(2)相互作用表面的残基在统计学上是共变的，这表明在该位点维持调节性蛋白质-蛋白质相互作用存在驱动力。总之，这些观察结果表明，像RecA和UmuD(2)这样的蛋白质可能在整个进化过程中负责控制DinB直系同源物的诱变潜力。
