Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
Environ Mol Mutagen. 2012 Dec;53(9):741-51. doi: 10.1002/em.21725. Epub 2012 Sep 18.
Chromosome breaks, often with damaged or missing DNA flanking the break site, are an important threat to genome stability. They are repaired in vertebrates primarily by nonhomologous end joining (NHEJ). NHEJ is unique among the major DNA repair pathways in that a continuous template cannot be used by DNA polymerases to instruct replacement of damaged or lost DNA. Nevertheless, at least 3 out of the 17 mammalian DNA polymerases are specifically employed by NHEJ. Biochemical and structural studies are further revealing how each of the polymerases employed by NHEJ possesses distinct and sophisticated means to overcome the barriers this pathway presents to polymerase activity. Still unclear, though, is how the resulting network of overlapping and nonoverlapping polymerase activities contributes to repair in cells.
染色体断裂，通常伴随着断裂部位周围受损或缺失的 DNA，是基因组稳定性的一个重要威胁。在脊椎动物中，它们主要通过非同源末端连接（NHEJ）进行修复。NHEJ 在主要的 DNA 修复途径中是独一无二的，因为 DNA 聚合酶不能使用连续的模板来指导受损或丢失的 DNA 的替换。然而，至少有 17 种哺乳动物 DNA 聚合酶中的 3 种被 NHEJ 特异性地利用。生化和结构研究进一步揭示了 NHEJ 所利用的每一种聚合酶如何具有独特而复杂的手段来克服该途径对聚合酶活性的障碍。然而，目前尚不清楚由此产生的聚合酶活性重叠和非重叠网络如何有助于细胞修复。
