Decoding the histone code: Role of H3K36me3 in mismatch repair and implications for cancer susceptibility and therapy.
Decoding the histone code: Role of H3K36me3 in mismatch repair and implications for cancer susceptibility and therapy.
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DOI：
10.1158/0008-5472.can-13-1870
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发表时间：
2013-11-01
期刊：
影响因子：
11.2
通讯作者：
Li GM
中科院分区：
文献类型：
--
作者：
Li GM
DNA错配修复（MMR）主要通过纠正复制相关的错配来维持基因组的稳定性。MMR缺陷导致几种人类癌症，其特征在于简单重复DNA序列的频繁改变，这种现象称为微卫星不稳定性（MSI）。在大多数MSI阳性癌症中，已经确定了改变必需MMR蛋白的功能或表达的遗传或表观遗传变化。然而，在MSI阳性癌症的子集中，在已知的MMR基因中尚未发现表观遗传或遗传变化，使得这些细胞中MMR缺陷的分子基础仍然未知。最近，当发现H3K36me3（一种经过充分研究的翻译后组蛋白修饰或组蛋白标记）在体内调节人类MMR中发挥作用时，这个难题的一个可能答案出现了。在这篇综述中，我们讨论了这种组蛋白标记在人类细胞中调节基因组稳定性和癌症易感性的潜在作用。
DNA mismatch repair (MMR) maintains genome stability primarily by correcting replication-associated mismatches. Defects in MMR lead to several human cancers characterized by frequent alterations in simple repetitive DNA sequences, a phenomenon called microsatellite instability (MSI). In most MSI-positive cancers, genetic or epigenetic changes that alter the function or expression of an essential MMR protein have been identified. However, in a subset of MSI-positive cancers, epigenetic or genetic changes have not been found in known MMR genes, such that the molecular basis of the MMR defect in these cells remains unknown. A possible answer to this puzzle emerged recently when it was discovered that H3K36me3, a well-studied post-translational histone modification or histone mark, plays a role in regulating human MMR in vivo. In this review, we discuss potential roles for this histone mark to modulate genome stability and cancer susceptibility in human cells.