Runge Kurt W, Li Yanhui
Department of Immunology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, NE20, Cleveland, OH, 44195, USA.
Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Curr Genet. 2018 Apr;64(2):359-364. doi: 10.1007/s00294-017-0760-1. Epub 2017 Oct 10.
Chromosomal breaks can be healed by several repair processes, including one called non-homologous end-joining (NHEJ) where the two broken ends are ligated together with a loss of 0-5 bp of DNA. The protein requirements for NHEJ of cut DNA ends in the budding yeast Saccharomyces cerevisiae include its version of the Mre11-Rad50-Nbs1 (MRN) complex. In contrast, the fission yeast Schizosaccharomyces pombe and mammalian cells do not require MRN for this process. Recent work in S. pombe used transposon excision to generate breaks that were capped by DNA hairpins, which must be opened to produce ligatable ends. Repair in S. pombe was through an NHEJ reaction that now requires MRN. Surprisingly, wild type cells and MRN mutants that lack nuclease activity showed the same levels of excision. These genetic results suggest that MRN recruits an unknown hairpin-opening nuclease for this unusual NHEJ reaction.
染色体断裂可以通过多种修复过程愈合，包括一种称为非同源末端连接（NHEJ）的过程，即两个断裂末端连接在一起，同时会丢失0至5个碱基对的DNA。在出芽酵母酿酒酵母中，切割DNA末端进行NHEJ所需的蛋白质包括其版本的Mre11-Rad50-Nbs1（MRN）复合物。相比之下，裂殖酵母粟酒裂殖酵母和哺乳动物细胞在此过程中不需要MRN。粟酒裂殖酵母最近的研究工作利用转座子切除产生由DNA发夹封闭的断裂，必须打开这些发夹才能产生可连接的末端。粟酒裂殖酵母中的修复是通过一种现在需要MRN的NHEJ反应进行的。令人惊讶的是，野生型细胞和缺乏核酸酶活性的MRN突变体表现出相同水平的切除。这些遗传学结果表明，MRN为这种不寻常的NHEJ反应招募了一种未知的发夹打开核酸酶。
