From the Departments of Internal Medicine and Molecular Genetics and Microbiology, University of New Mexico Comprehensive Cancer Center, University of New Mexico, Albuquerque, New Mexico 87131.
From the Departments of Internal Medicine and Molecular Genetics and Microbiology, University of New Mexico Comprehensive Cancer Center, University of New Mexico, Albuquerque, New Mexico 87131
J Biol Chem. 2018 Jul 6;293(27):10536-10546. doi: 10.1074/jbc.TM117.000375. Epub 2018 Mar 12.
Alternative end-joining (a-EJ) pathways, which repair DNA double-strand breaks (DSBs), are initiated by end resection that generates 3' single strands. This reaction is shared, at least in part, with homologous recombination but distinguishes a-EJ from the major nonhomologous end-joining pathway. Although the a-EJ pathways make only a minor and poorly understood contribution to DSB repair in nonmalignant cells, there is growing interest in these pathways, as they generate genomic rearrangements that are hallmarks of cancer cells. Here, we review and discuss the current understanding of the mechanisms and regulation of a-EJ pathways, the role of a-EJ in human disease, and the potential utility of a-EJ as a therapeutic target in cancer.
非同源末端连接（a-EJ）途径通过末端切除起始修复 DNA 双链断裂（DSBs），产生 3'单链。该反应至少部分与同源重组共享，但将 a-EJ 与主要的非同源末端连接途径区分开来。虽然 a-EJ 途径在非恶性细胞的 DSB 修复中仅做出轻微且理解不佳的贡献，但人们对这些途径的兴趣日益浓厚，因为它们产生了癌症细胞的标志性基因组重排。在这里，我们回顾和讨论了对 a-EJ 途径的机制和调节、a-EJ 在人类疾病中的作用以及 a-EJ 作为癌症治疗靶点的潜在效用的当前理解。
