The Tale of CHD4 in DNA Damage Response and Chemotherapeutic Response

Shiaw-Yih Lin,David J.H Shih,Jing Zhang

doi:10.31579/2640-1053/052

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.

Highlights

Known as Mi2β, Chromodomain helicase DNA-binding 4 (CHD4), a highly conserved protein (~250 kDa) in animals and plants [1], is one of members of the SNF2/RAD54 helicase family, which use the energy derived from ATP hydrolysis to remodel nucleosome structure [2, 3]
CHD4 serves as a key component of the nucleosome remodeling and deacetylase (NuRD) complex, which plays an important role in regulation of chromatin structure, gene expression, and cell cycle progression during normal development and tumorigenesis [5, 6]
We previously reported that CHD4 depletion and CHD4 mutations promote endometrial cancer stemness by activating TGF-beta signaling [23]

Summary

Review Article

Jing Zhang, David J.H. Shih and Shiaw-Yih Lin1* 1Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. Received date: June 20, 2019; Accepted date : July 05, 2019; Published date: July 08, 2019. Citation : Jing Zhang, David J.H. Shih and Shiaw-Yih Lin. The Tale of CHD4 in DNA Damage Response and Chemotherapeutic Response, J.

Introduction

Findings

Conclusion and future directions