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题名: HSF4 is involved in DNA damage repair through regulation of Rad51
作者: Cui, Xiukun1; Zhang, Jing1, 2; Du, Rong3; Wang, Lei1; Archacki, Stephen4, 5; Zhang, Yuexuan1; Yuan, Mingxiong1; Ke, Tie1; Li, Hui1; Li, Duanzhuo1; Li, Chang1; Li, David Wan-Cheng6; Tang, Zhaohui1; Yin, Zhan1, 2; Liu, Mugen1
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.
关键词: Cataract ; HSF4 ; DNA damage ; Rad51 ; Camptothecin
刊名: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
发表日期: 2012-08-01
DOI: 10.1016/j.bbadis.2012.05.005
卷: 1822, 期:8, 页:1308-1315
收录类别: SCI
文章类型: Article
部门归属: [Cui, Xiukun; Zhang, Jing; Wang, Lei; Zhang, Yuexuan; Yuan, Mingxiong; Ke, Tie; Li, Hui; Li, Duanzhuo; Li, Chang; Tang, Zhaohui; Yin, Zhan; Liu, Mugen] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Ctr Human Genome Res, Key Lab Mol Biophys,Minist Educ, Wuhan 430074, Hubei, Peoples R China; [Zhang, Jing; Yin, Zhan] Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China; [Du, Rong] Huazhong Univ Sci & Technol, Union Hosp, Wuhan 430022, Hubei, Peoples R China; [Archacki, Stephen] Cleveland Clin Fdn, Dept Mol Cardiol, Ctr Cardiovasc Genet, Cleveland, OH 44195 USA; [Archacki, Stephen] Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA; [Li, David Wan-Cheng] Univ Nebraska Med Ctr, Coll Med, Dept Biochem & Mol Biol, Omaha, NE 68198 USA
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: National Natural Science Foundation of China[30871386, 31071166, 30800459, 30771199]
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
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.
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.
关键词[WOS]: LENS EPITHELIAL-CELLS ; HOMOLOGOUS RECOMBINATION REPAIR ; TRANSCRIPTION FACTOR ; TOPOISOMERASE-I ; GENES XPD ; CATARACT ; DIFFERENTIATION ; STRESS ; BREAKS ; NBS1
语种: 英语
WOS记录号: WOS:000306032800015
ISSN号: 0925-4439
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/17013
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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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

Recommended Citation:
Cui, Xiukun; Zhang, Jing; Du, Rong; Wang, Lei; Archacki, Stephen; Zhang, Yuexuan; Yuan, Mingxiong; Ke, Tie; Li, Hui; Li, Duanzhuo; Li, Chang; Li, David Wan-Cheng; Tang, Zhaohui; Yin, Zhan; Liu, Mugen.HSF4 is involved in DNA damage repair through regulation of Rad51,BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,2012,1822(8):1308-1315
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