Involvement of DNA mismatch repair in the maintenance of heterochromatic DNA stability in Saccharomyces cerevisiae.
Involvement of DNA mismatch repair in the maintenance of heterochromatic DNA stability in Saccharomyces cerevisiae.
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DOI：
10.1371/journal.pgen.1007074
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发表时间：
2017-10
期刊：
影响因子：
4.5
通讯作者：
Kadyrov FA
中科院分区：
文献类型：
--
作者：
Dahal BK;Kadyrova LY;Delfino KR;Rogozin IB;Gujar V;Lobachev KS;Kadyrov FA
异染色质含有核DNA的重要部分。关于异染色质DNA稳定性的机制知之甚少。我们发现在酿酒酵母中，（i）DNA错配修复（MMR）是维持异染色质DNA稳定性所必需的，（ii）MutLα（Mlh 1-Pms 1异源二聚体），MutSα（Msh 2-Msh 6异二聚体），MutSβ（iii）异染色质处的Exo 1非依赖性MMR经常导致Pol β依赖性突变的形成，（iv）MMR与Pol ε和组蛋白乙酰转移酶Rtt 109的校对活性合作维持异染色质DNA稳定性，（v）异染色质处碱基-碱基错配的修复不如常染色质处碱基-碱基错配的修复有效，和（vi）异染色质上1-nt插入/缺失环的修复效率与1-nt插入/缺失环的修复效率相似。常染色质缺失环。真核细胞错配修复是一个重要的细胞内过程，保护DNA免受突变。人类细胞中错配修复的失活大大增加了癌症发生和发展的风险。虽然在理解常染色质的错配修复方面已经取得了重大进展，但异染色质的错配修复还没有得到很好的理解。面包酵母是研究错配修复的重要模式生物。我们确定在面包酵母中（1）错配修复保护异染色质DNA免于突变，（2）MutLα、MutSα、MutSβ和Exo 1蛋白在异染色质错配修复中起重要作用，（3）异染色质上不依赖Exo 1的错配修复是一个容易出错的过程，（4）错配修复与其他两个胞内过程协同作用以保护异染色质DNA的稳定性，（5）错配修复与其他两个胞内过程协同作用以保护异染色质DNA的稳定性。和（5）异染色质上碱基-碱基错配的修复效率低于常染色质上碱基-碱基错配的修复效率，但异染色质上1-nt插入/缺失环的修复效率与常染色质上1-nt插入/缺失环的修复效率相似。
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. Eukaryotic mismatch repair is an important intracellular process that defends DNA against mutations. Inactivation of mismatch repair in human cells strongly increases the risk of cancer initiation and development. Although significant progress has been made in understanding mismatch repair at euchromatin, mismatch repair at heterochromatin is not well understood. Baker’s yeast is a key model organism to study mismatch repair. We determined that in baker’s yeast (1) mismatch repair protects heterochromatic DNA from mutations, (2) the MutLα, MutSα, MutSβ, and Exo1 proteins play important roles in mismatch repair at heterochromatin, (3) Exo1-independent mismatch repair at heterochromatin is an error-prone process; (4) mismatch repair cooperates with two other intracellular processes to protect the stability of heterochromatic DNA; and (5) the efficiency of repair of base-base mismatches at heterochromatin is lower than the efficiency of repair of base-base mismatches at euchromatin, but the efficiency of 1-nt insertion/deletion loop repair at heterochromatin is similar to the efficiency of 1-nt insertion/deletion loop repair at euchromatin.
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DOI：
10.1126/science.1135862
发表时间：
2007-02-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Driscoll R;Hudson A;Jackson SP
通讯作者：
Jackson SP
影响因子：
16
作者：
Ghodgaonkar, Medini Manohar;Lazzaro, Federico;Olivera-Pimentel, Maite;Artola-Boran, Mariela;Cejka, Petr;Reijns, Martin A.;Jackson, Andrew P.;Plevani, Paolo;Muzi-Falconi, Marco;Jiricny, Josef
通讯作者：
Jiricny, Josef
影响因子：
56.9
作者：
DRUMMOND, JT;LI, GM;MODRICH, P
通讯作者：
MODRICH, P
影响因子：
4.8
作者：
Blanko, Elena Rodriges;Kadyrova, Lyudmila Y.;Kadyrov, Farid A.
通讯作者：
Kadyrov, Farid A.
影响因子：
4.8
作者：
Genschel, J;Bazemore, LR;Modrich, P
通讯作者：
Modrich, P