Goellner Eva M, Putnam Christopher D, Kolodner Richard D
Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92093-0669, USA.
Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92093-0669, USA; Departments of Medicine, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0669, USA.
DNA Repair (Amst). 2015 Aug;32:24-32. doi: 10.1016/j.dnarep.2015.04.010. Epub 2015 Apr 30.
DNA mismatch repair (MMR) acts to repair mispaired bases resulting from misincorporation errors during DNA replication and also recognizes mispaired bases in recombination (HR) intermediates. Exonuclease 1 (Exo1) is a 5' → 3' exonuclease that participates in a number of DNA repair pathways. Exo1 was identified as an exonuclease that participates in Saccharomyces cerevisiae and human MMR where it functions to excise the daughter strand after mispair recognition, and additionally Exo1 functions in end resection during HR. However, Exo1 is not absolutely required for end resection during HR in vivo. Similarly, while Exo1 is required in MMR reactions that have been reconstituted in vitro, genetics studies have shown that it is not absolutely required for MMR in vivo suggesting the existence of Exo1-independent and Exo1-dependent MMR subpathways. Here, we review what is known about the Exo1-independent and Exo1-dependent subpathways, including studies of mutations in MMR genes that specifically disrupt either subpathway.
DNA错配修复(MMR)可修复DNA复制过程中因错误掺入而产生的错配碱基,还能识别重组(HR)中间体中的错配碱基。核酸外切酶1(Exo1)是一种5'→3'核酸外切酶,参与多种DNA修复途径。Exo1被鉴定为参与酿酒酵母和人类MMR的核酸外切酶,在错配识别后,它负责切除子链,此外,Exo1在HR过程中的末端切除中发挥作用。然而,在体内HR过程中,末端切除并非绝对需要Exo1。同样,虽然在体外重建的MMR反应中需要Exo1,但遗传学研究表明,在体内MMR过程中Exo1并非绝对必需,这表明存在不依赖Exo1和依赖Exo1的MMR子途径。在此,我们综述了关于不依赖Exo1和依赖Exo1的子途径的已知信息,包括对MMR基因中特异性破坏任一子途径的突变的研究。