Dahal Basanta K, Kadyrova Lyudmila Y, Delfino Kristin R, Rogozin Igor B, Gujar Vaibhavi, Lobachev Kirill S, Kadyrov Farid A
Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL, United States of America.
Center for Clinical Research, Southern Illinois University School of Medicine, Springfield, IL, United States of America.
PLoS Genet. 2017 Oct 25;13(10):e1007074. doi: 10.1371/journal.pgen.1007074. eCollection 2017 Oct.
Heterochromatin contains a significant part of nuclear DNA. Little is known about the mechanisms that govern heterochromatic DNA stability. We show here that in the yeast Saccharomyces cerevisiae (i) DNA mismatch repair (MMR) is required for the maintenance of heterochromatic DNA stability, (ii) MutLα (Mlh1-Pms1 heterodimer), MutSα (Msh2-Msh6 heterodimer), MutSβ (Msh2-Msh3 heterodimer), and Exo1 are involved in MMR at heterochromatin, (iii) Exo1-independent MMR at heterochromatin frequently leads to the formation of Pol ζ-dependent mutations, (iv) MMR cooperates with the proofreading activity of Pol ε and the histone acetyltransferase Rtt109 in the maintenance of heterochromatic DNA stability, (v) repair of base-base mismatches at heterochromatin is less efficient than repair of base-base mismatches at euchromatin, and (vi) the efficiency of repair of 1-nt insertion/deletion loops at heterochromatin is similar to the efficiency of repair of 1-nt insertion/deletion loops at euchromatin.
异染色质包含了细胞核DNA的很大一部分。关于调控异染色质DNA稳定性的机制，我们所知甚少。我们在此表明，在酿酒酵母中：（i）DNA错配修复（MMR）是维持异染色质DNA稳定性所必需的；（ii）MutLα（Mlh1 - Pms1异二聚体）、MutSα（Msh2 - Msh6异二聚体）、MutSβ（Msh2 - Msh3异二聚体）和Exo1参与了异染色质处的MMR；（iii）异染色质处不依赖Exo1的MMR经常导致形成依赖Pol ζ的突变；（iv）MMR与Pol ε的校对活性以及组蛋白乙酰转移酶Rtt109协同作用以维持异染色质DNA稳定性；（v）异染色质处碱基错配的修复效率低于常染色质处碱基错配的修复效率；（vi）异染色质处1个核苷酸插入/缺失环的修复效率与常染色质处1个核苷酸插入/缺失环的修复效率相似。
