Kadyrova Lyudmila Y, Kadyrov Farid A
Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA.
Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA.
DNA Repair (Amst). 2016 Feb;38:42-49. doi: 10.1016/j.dnarep.2015.11.023. Epub 2015 Dec 2.
MutLα is a key component of the DNA mismatch repair system in eukaryotes. The DNA mismatch repair system has several genetic stabilization functions. Of these functions, DNA mismatch repair is the major one. The loss of MutLα abolishes DNA mismatch repair, thereby predisposing humans to cancer. MutLα has an endonuclease activity that is required for DNA mismatch repair. The endonuclease activity of MutLα depends on the DQHA(X)2E(X)4E motif which is a part of the active site of the nuclease. This motif is also present in many bacterial MutL and eukaryotic MutLγ proteins, DNA mismatch repair system factors that are homologous to MutLα. Recent studies have shown that yeast MutLγ and several MutL proteins containing the DQHA(X)2E(X)4E motif possess endonuclease activities. Here, we review the endonuclease activities of MutLα and its homologs in the context of DNA mismatch repair.
MutLα是真核生物DNA错配修复系统的关键组成部分。DNA错配修复系统具有多种基因稳定功能。在这些功能中，DNA错配修复是主要功能。MutLα的缺失会导致DNA错配修复功能丧失，从而使人类易患癌症。MutLα具有DNA错配修复所需的内切核酸酶活性。MutLα的内切核酸酶活性依赖于DQHA(X)2E(X)4E基序，该基序是核酸酶活性位点的一部分。这个基序也存在于许多细菌MutL和真核生物MutLγ蛋白中，它们是与MutLα同源的DNA错配修复系统因子。最近的研究表明，酵母MutLγ和几种含有DQHA(X)2E(X)4E基序的MutL蛋白具有内切核酸酶活性。在这里，我们在DNA错配修复的背景下综述MutLα及其同源物的内切核酸酶活性。
