Polyzos Aris A, McMurray Cynthia T
MBIB Division, Lawrence Berkeley Laboratory, 1 Cyclotron Rd., Berkeley, CA 94720, United States.
MBIB Division, Lawrence Berkeley Laboratory, 1 Cyclotron Rd., Berkeley, CA 94720, United States.
DNA Repair (Amst). 2017 Aug;56:144-155. doi: 10.1016/j.dnarep.2017.06.017. Epub 2017 Jun 9.
Expansion of simple triplet repeats (TNR) underlies more than 30 severe degenerative diseases. There is a good understanding of the major pathways generating an expansion, and the associated polymerases that operate during gap filling synthesis at these "difficult to copy" sequences. However, the mechanism by which a TNR is repaired depends on the type of lesion, the structural features imposed by the lesion, the assembled replication/repair complex, and the polymerase that encounters it. The relationships among these parameters are exceptionally complex and how they direct pathway choice is poorly understood. In this review, we consider the properties of polymerases, and how encounters with GC-rich or abnormal structures might influence polymerase choice and the success of replication and repair. Insights over the last three years have highlighted new mechanisms that provide interesting choices to consider in protecting genome stability.
简单三联体重复序列（TNR）的扩增是30多种严重退行性疾病的基础。目前对产生扩增的主要途径以及在这些“难以复制”序列的缺口填补合成过程中起作用的相关聚合酶有了很好的了解。然而，TNR的修复机制取决于损伤的类型、损伤所施加的结构特征、组装的复制/修复复合体以及遇到它的聚合酶。这些参数之间的关系异常复杂，人们对它们如何指导途径选择知之甚少。在这篇综述中，我们考虑了聚合酶的特性，以及与富含GC的结构或异常结构的相遇如何可能影响聚合酶的选择以及复制和修复的成功。过去三年的见解突出了新的机制，这些机制为保护基因组稳定性提供了有趣的选择。
