Interplay between mismatch repair and chromatin assembly
Interplay between mismatch repair and chromatin assembly
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DOI：
10.1073/pnas.1106696109
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发表时间：
2012-02-07
影响因子：
11.1
通讯作者：
Jiricny, Josef
中科院分区：
文献类型：
--
作者：
Schoepf, Barbara;Bregenhorn, Stephanie;Jiricny, Josef
据报道，DNA中的单链刻痕和间隙可以提高染色质组装因子1 （caf1）介导的核小体装载效率。然而，在含有错配的底物上，这些链的不连续性被错配修复（MMR）系统用作核酸外切酶1的装载位点，在那里含有错配的链开始降解。由于将DNA包装成染色质可能会抑制MMR，我们有兴趣了解染色质组装在异双工和同双工底物上是否受到不同的调节。我们现在表明，在一个缺口质粒底物错配的存在延迟核小体装载在人类细胞提取物。我们的数据还表明，一旦不匹配被移除，单链间隙的修复伴随着有效的核小体装载。我们假设MMR和染色质组装之间的平衡可能由增殖细胞核抗原（PCNA）控制，PCNA是复制DNA聚合酶的加工因子，装载在DNA末端，并与错配识别因子MutS α的MSH6亚基以及ca -1相互作用。我们现在表明，这种监管可能更复杂；MutS α和ca -1不仅与PCNA相互作用，还相互作用。在体内，这种相互作用在s期增加，并可能受ca -1的p150亚基的磷酸化状态控制。
Single strand nicks and gaps in DNA have been reported to increase the efficiency of nucleosome loading mediated by chromatin assembly factor 1 (CAF-1). However, on mismatch-containing substrates, these strand discontinuities are utilized by the mismatch repair (MMR) system as loading sites for exonuclease 1, at which degradation of the error-containing strand commences. Because packaging of DNA into chromatin might inhibit MMR, we were interested to learn whether chromatin assembly is differentially regulated on heteroduplex and homoduplex substrates. We now show that the presence of a mismatch in a nicked plasmid substrate delays nucleosome loading in human cell extracts. Our data also suggest that, once the mismatch is removed, repair of the single-stranded gap is accompanied by efficient nucleosome loading. We postulated that the balance between MMR and chromatin assembly might be governed by proliferating cell nuclear antigen (PCNA), the processivity factor of replicative DNA polymerases, which is loaded at DNA termini and which interacts with the MSH6 subunit of the mismatch recognition factor MutS alpha, as well as with CAF-1. We now show that this regulation might be more complex; MutS alpha and CAF-1 interact not only with PCNA, but also with each other. In vivo this interaction increases during S-phase and may be controlled by the phosphorylation status of the p150 subunit of CAF-1.