The Tale of CHD4 in DNA Damage Response and Chemotherapeutic Response.

Journal of cancer research and cellular therapeutics Pub Date : 2019-01-01 Epub Date: 2019-07-08
Jing Zhang, David J H Shih, Shiaw-Yih Lin
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Abstract

The chromatin remodeling factor chromodomain helicase DNA-binding protein 4 (CHD4) is a core component of the nucleosome remodeling and deacetylase (NuRD) complex. Due to its important role in DNA damage repair, CHD4 has been identified as a key determinant in cancer progression, stem cell differentiation, and T cell and B cell development. Accumulating evidence has revealed that CHD4 can function in NuRD dependent and independent manner in response to DNA damage. Mutations of CHD4 have been shown to diminish its functions, which indicates that interpretation of its mutations may provide tangible benefit for patients. The expression of CHD4 play a dual role in sensitizing cancer cells to chemotherapeutic agents, which provides new insights into the contribution of CHD4 to tumor biology and new therapeutic avenues.

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CHD4在DNA损伤反应和化疗反应中的作用。
染色质重塑因子染色质结构域解旋酶dna结合蛋白4 (CHD4)是核小体重塑和去乙酰化酶(NuRD)复合物的核心成分。由于其在DNA损伤修复中的重要作用,CHD4已被确定为癌症进展、干细胞分化、T细胞和B细胞发育的关键决定因素。越来越多的证据表明,CHD4可以以NuRD依赖和独立的方式响应DNA损伤。CHD4的突变已被证明会削弱其功能,这表明对其突变的解释可能会为患者提供切实的益处。CHD4的表达在肿瘤细胞对化疗药物的敏感性中起着双重作用,这为CHD4在肿瘤生物学中的贡献和新的治疗途径提供了新的见解。
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