Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115, USA; email:
Annu Rev Biochem. 2021 Jun 20;90:137-164. doi: 10.1146/annurev-biochem-080320-110356. Epub 2021 Feb 8.
DNA double-strand breaks pose a serious threat to genome stability. In vertebrates, these breaks are predominantly repaired by nonhomologous end joining (NHEJ), which pairs DNA ends in a multiprotein synaptic complex to promote their direct ligation. NHEJ is a highly versatile pathway that uses an array of processing enzymes to modify damaged DNA ends and enable their ligation. The mechanisms of end synapsis and end processing have important implications for genome stability. Rapid and stable synapsis is necessary to limit chromosome translocations that result from the mispairing of DNA ends. Furthermore, end processing must be tightly regulated to minimize mutations at the break site. Here, we review our current mechanistic understanding of vertebrate NHEJ, with a particular focus on end synapsis and processing.
DNA 双链断裂对基因组稳定性构成严重威胁。在脊椎动物中，这些断裂主要通过非同源末端连接（NHEJ）修复，该过程将 DNA 末端配对到多蛋白突触复合物中，以促进其直接连接。NHEJ 是一种高度多功能的途径，它使用一系列加工酶来修饰受损的 DNA 末端，并使其能够连接。末端连接和末端加工的机制对基因组稳定性具有重要意义。快速和稳定的连接对于限制由于 DNA 末端错配导致的染色体易位是必要的。此外，末端加工必须受到严格控制，以最大限度地减少断裂部位的突变。在这里，我们回顾了我们目前对脊椎动物 NHEJ 的机制理解，特别关注末端连接和加工。
