Nucleosomes around a mismatched base pair are excluded via an Msh2-dependent reaction with the aid of SNF2 family ATPase Smarcad1.
Nucleosomes around a mismatched base pair are excluded via an Msh2-dependent reaction with the aid of SNF2 family ATPase Smarcad1.
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DOI：
10.1101/gad.310995.117
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发表时间：
2018-06-01
影响因子：
10.5
通讯作者：
Takahashi TS
中科院分区：
文献类型：
--
作者：
Terui R;Nagao K;Kawasoe Y;Taki K;Higashi TL;Tanaka S;Nakagawa T;Obuse C;Masukata H;Takahashi TS
在这里，Terui等人。研究了在MMR过程中发生染色质重塑的机制。他们表明，真核MMR系统具有排除局部核小体的能力，并将Smarcad1/Fun30鉴定为MMR反应的辅助因子。错配修复(MMR)系统对复制错误的复制后纠正是抑制突变的关键。尽管MMR系统可能需要在染色质复制位置处理核小体，但MMR如何在染色质环境中发生仍不清楚。在这里，我们表明，核小体被排除在非洲爪哇卵子提取物中不匹配的碱基对周围的>；1-kb区域。这种排除依赖于Msh2-MSH6错配识别复合体，而不是含有MLH1的MutL同源物，并抵消了HIRA和CAF-1(染色质组装因子1)介导的染色质组装途径。我们进一步发现，Smarcad1染色质重塑ATPase以Msh2依赖但MLH1不依赖的方式被招募到错配携带DNA，以帮助核小体排除，并且当核小体预先组装在DNA上时，Smarcad1促进错配修复。在芽殖酵母中，SMARCAD1的同源物FUN30的缺失与MSH6或MSH3的缺失一起显示出自发突变的协同增加，而与MSH2的缺失没有显著的协同作用。遗传分析还表明，Fun30在MMR中的功能是中和CAF-1。我们的研究发现，真核MMR系统具有排除局部核小体的能力，并发现Smarcad1/Fun30是MMR反应的辅助因子。
Here, Terui et al. studied the mechanisms underlying chromatin remodeling that occurs during MMR. They show that the eukaryotic MMR system has an ability to exclude local nucleosomes and identify Smarcad1/Fun30 as an accessory factor for the MMR reaction. Post-replicative correction of replication errors by the mismatch repair (MMR) system is critical for suppression of mutations. Although the MMR system may need to handle nucleosomes at the site of chromatin replication, how MMR occurs in the chromatin environment remains unclear. Here, we show that nucleosomes are excluded from a >1-kb region surrounding a mismatched base pair in Xenopus egg extracts. The exclusion was dependent on the Msh2–Msh6 mismatch recognition complex but not the Mlh1-containing MutL homologs and counteracts both the HIRA- and CAF-1 (chromatin assembly factor 1)-mediated chromatin assembly pathways. We further found that the Smarcad1 chromatin remodeling ATPase is recruited to mismatch-carrying DNA in an Msh2-dependent but Mlh1-independent manner to assist nucleosome exclusion and that Smarcad1 facilitates the repair of mismatches when nucleosomes are preassembled on DNA. In budding yeast, deletion of FUN30, the homolog of Smarcad1, showed a synergistic increase of spontaneous mutations in combination with MSH6 or MSH3 deletion but no significant increase with MSH2 deletion. Genetic analyses also suggested that the function of Fun30 in MMR is to counteract CAF-1. Our study uncovers that the eukaryotic MMR system has an ability to exclude local nucleosomes and identifies Smarcad1/Fun30 as an accessory factor for the MMR reaction.
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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：
64.8
作者：
Costelloe, Thomas;Louge, Raphael;Tomimatsu, Nozomi;Mukherjee, Bipasha;Martini, Emmanuelle;Khadaroo, Basheer;Dubois, Kenny;Wiegant, Wouter W.;Thierry, Agnes;Burma, Sandeep;van Attikum, Haico;Llorente, Bertrand
通讯作者：
Llorente, Bertrand
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：
7
作者：
Chen, Zhen;Tran, Mykim;Chen, Junjie
通讯作者：
Chen, Junjie
DOI：
10.1016/j.bbagrm.2011.07.009
发表时间：
2012-03
影响因子：
4.7
作者：
Formosa, Tim
通讯作者：
Formosa, Tim