DNA损伤应答与化疗应答中的CHD4故事
The Tale of CHD4 in DNA Damage Response and Chemotherapeutic Response.
作者信息
Zhang Jing, Shih David J H, Lin Shiaw-Yih
机构信息
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
出版信息
J Cancer Res Cell Ther. 2019;3(1). Epub 2019 Jul 8.
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.
摘要
染色质重塑因子染色质结构域解旋酶DNA结合蛋白4（CHD4）是核小体重塑去乙酰化酶（NuRD）复合物的核心组成部分。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、干细胞分化以及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可通过依赖NuRD和不依赖NuRD的方式对DNA损伤作出反应。已证实CHD4的突变会削弱其功能，这表明对其突变的解读可能为患者带来切实益处。CHD4的表达在使癌细胞对化疗药物敏感方面具有双重作用，这为CHD4对肿瘤生物学的贡献及新的治疗途径提供了新见解。
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