HSF4 is involved in DNA damage repair through regulation of Rad51

doi:10.1016/j.bbadis.2012.05.005

CORC > 水生生物研究所 > 中科院水生所知识产出（2009年前） > 水生生物分子与细胞生物学研究中心 > 期刊论文

	HSF4 is involved in DNA damage repair through regulation of Rad51
	Cui, Xiukun 1; Zhang, Jing 1,2; Du, Rong 3; Wang, Lei 1; Archacki, Stephen 4,5; Zhang, Yuexuan 1; Yuan, Mingxiong 1; Ke, Tie 1; Li, Hui 1; Li, Duanzhuo 1
刊名	BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
	2012-08-01
卷号	1822 期号:8 页码:1308-1315
关键词	Cataract Hsf4 Dna Damage Rad51 Camptothecin
ISSN号	0925-4439
DOI	10.1016/j.bbadis.2012.05.005
文献子类	Article
英文摘要	Heat shock factor protein 4 (HSF4) is expressed exclusively in the ocular lens and plays a critical role in the lens formation and differentiation. Mutations in the HSF4 gene lead to congenital and senile cataract. However, the molecular mechanisms causing this disease have not been well characterized. DNA damage in lens is a crucial risk factor in senile cataract formation, and its timely repair is essential for maintaining the lens' transparency. Our study firstly found evidence that HSF4 contributes to the repair of DNA strand breaks. Yet, this does not occur with cataract causative mutations in HSF4. We verify that DNA damage repair is mediated by the binding of HSF4 to a heat shock element in the Rad51 promoter, a gene which assists in the homologous recombination (HR) repair of DNA strand breaks. HSF4 up-regulates Rad51 expression while mutations in HSF4 fail, and DNA does not get repaired. Camptothecin, which interrupts the regulation of Rad51 by HSF4, also affects DNA damage repair. Additionally, with HSF4 knockdown in the lens of Zebrafish, DNA damage was observed and the protein level of Rad51 was significantly lower. Our study presents the first evidence demonstrating that HSF4 plays a role in DNA damage repair and may contribute a better understanding of congenital cataract formation. (C) 2012 Elsevier B.V. All rights reserved.; Heat shock factor protein 4 (HSF4) is expressed exclusively in the ocular lens and plays a critical role in the lens formation and differentiation. Mutations in the HSF4 gene lead to congenital and senile cataract. However, the molecular mechanisms causing this disease have not been well characterized. DNA damage in lens is a crucial risk factor in senile cataract formation, and its timely repair is essential for maintaining the lens' transparency. Our study firstly found evidence that HSF4 contributes to the repair of DNA strand breaks. Yet, this does not occur with cataract causative mutations in HSF4. We verify that DNA damage repair is mediated by the binding of HSF4 to a heat shock element in the Rad51 promoter, a gene which assists in the homologous recombination (HR) repair of DNA strand breaks. HSF4 up-regulates Rad51 expression while mutations in HSF4 fail, and DNA does not get repaired. Camptothecin, which interrupts the regulation of Rad51 by HSF4, also affects DNA damage repair. Additionally, with HSF4 knockdown in the lens of Zebrafish, DNA damage was observed and the protein level of Rad51 was significantly lower. Our study presents the first evidence demonstrating that HSF4 plays a role in DNA damage repair and may contribute a better understanding of congenital cataract formation. (C) 2012 Elsevier B.V. All rights reserved.
WOS关键词	LENS EPITHELIAL-CELLS ; HOMOLOGOUS RECOMBINATION REPAIR ; TRANSCRIPTION FACTOR ; TOPOISOMERASE-I ; GENES XPD ; CATARACT ; DIFFERENTIATION ; STRESS ; BREAKS ; NBS1
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
语种	英语
WOS记录号	WOS:000306032800015
资助机构	National Natural Science Foundation of China[30871386, 31071166, 30800459, 30771199] ; National Natural Science Foundation of China[30871386, 31071166, 30800459, 30771199] ; National Natural Science Foundation of China[30871386, 31071166, 30800459, 30771199] ; National Natural Science Foundation of China[30871386, 31071166, 30800459, 30771199]
公开日期	2012-09-25
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/17013]
专题	水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文
通讯作者	Liu, MG (reprint author), Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Ctr Human Genome Res, Key Lab Mol Biophys,Minist Educ, 1037 Luoyu Rd, Wuhan 430074, Hubei, Peoples R China.
作者单位	1.Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Ctr Human Genome Res, Key Lab Mol Biophys,Minist Educ, Wuhan 430074, Hubei, Peoples R China 2.Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China 3.Huazhong Univ Sci & Technol, Union Hosp, Wuhan 430022, Hubei, Peoples R China 4.Cleveland Clin Fdn, Dept Mol Cardiol, Ctr Cardiovasc Genet, Cleveland, OH 44195 USA 5.Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA 6.Univ Nebraska Med Ctr, Coll Med, Dept Biochem & Mol Biol, Omaha, NE 68198 USA
推荐引用方式 GB/T 7714	Cui, Xiukun,Zhang, Jing,Du, Rong,et al. HSF4 is involved in DNA damage repair through regulation of Rad51[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,2012,1822(8):1308-1315.
APA	Cui, Xiukun.,Zhang, Jing.,Du, Rong.,Wang, Lei.,Archacki, Stephen.,...&Liu, MG .(2012).HSF4 is involved in DNA damage repair through regulation of Rad51.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,1822(8),1308-1315.
MLA	Cui, Xiukun,et al."HSF4 is involved in DNA damage repair through regulation of Rad51".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 1822.8(2012):1308-1315.