Histone deacetylases 1 and 2 regulate DNA replication and DNA repair: potential targets for genome stability-mechanism-based therapeutics for a subset of cancers.
Histone deacetylases 1 and 2 regulate DNA replication and DNA repair: potential targets for genome stability-mechanism-based therapeutics for a subset of cancers.
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DOI：
10.1080/15384101.2015.1042634
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Bhaskara S
中科院分区：
文献类型：
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作者：
Bhaskara S
组蛋白去乙酰化酶1和2（HDAC 1，2）属于I类HDAC家族，其被目前用于癌症治疗的FDA批准的小分子HDAC抑制剂靶向。HDAC1，2在DNA修复过程中被募集到DNA断裂位点，在DNA复制过程中被募集到叉周围的染色质。癌细胞利用DNA修复和DNA复制作为生存机制，并逃避化疗诱导的细胞毒性。因此，了解HDAC 1，2在基因组维持过程（DNA复制和DNA修复）中的功能是至关重要的，以便深入了解HDAC抑制剂在癌症治疗中的作用模式。一流的HDAC1，2选择性抑制剂和Hdac1，2条件性敲除系统极大地促进了HDAC1，2控制正常和癌细胞中基因组稳定性的精确机制的剖析。从这个角度来看，我总结了关于I类HDAC的机制功能的发现，特别是HDAC1，2在基因组维护中，未来研究的未回答问题以及如何利用这些知识更好地靶向癌症治疗癌症的观点。
Histone deacetylases 1 and 2 (HDAC1,2) belong to the class I HDAC family, which are targeted by the FDA-approved small molecule HDAC inhibitors currently used in cancer therapy. HDAC1,2 are recruited to DNA break sites during DNA repair and to chromatin around forks during DNA replication. Cancer cells use DNA repair and DNA replication as survival mechanisms and to evade chemotherapy-induced cytotoxicity. Hence, it is vital to understand how HDAC1,2 function during the genome maintenance processes (DNA replication and DNA repair) in order to gain insights into the mode-of-action of HDAC inhibitors in cancer therapeutics. The first-in-class HDAC1,2-selective inhibitors and Hdac1,2 conditional knockout systems greatly facilitated dissecting the precise mechanisms by which HDAC1,2 control genome stability in normal and cancer cells. In this perspective, I summarize the findings on the mechanistic functions of class I HDACs, specifically, HDAC1,2 in genome maintenance, unanswered questions for future investigations and views on how this knowledge could be harnessed for better-targeted cancer therapeutics for a subset of cancers.