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	Zebrafish Mms2 promotes K63-linked polyubiquitination and is involved in p53-mediated DNA-damage response
	Wen, Rui2,3; Li, Jie1; Xu, Xin2; Cui, Zongbin1; Xiao, Wei2,3; Cui, ZB (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China.
刊名	DNA REPAIR
	2012-02-01
卷号	11期号:2页码:157-166
关键词	Zebrafish Ubc13 Mms2 K63-linked Polyubiquitination Dna-damage Tolerance P53
ISSN号	1568-7864
DOI	10.1016/j.dnarep.2011.10.015
文献子类	Article
英文摘要	The ubiquitin-conjugating enzyme Ubc13 together with a Ubc/E2 variant (Uev) form a stable complex and mediate K63-linked polyubiquitination, which is implicated in DNA damage tolerance in yeast and mammalian cells. The zebrafish Danio rerio is a lower vertebrate model organism widely used in the studies of vertebrate development and environmental stress responses. Here we report the identification and functional characterization of two zebrafish UEV genes, Drmms2 and Druev1. Their deduced amino acid sequences indicate that the two UEV genes evolved separately prior to the appearance of vertebrates. Both zebrafish Uevs form a stable complex with DrUbc13 as well as Ubc13s from yeast and human, and are able to promote Ubc13-mediated K63 polyubiquitination in vitro, suggesting that their biochemical activities are conserved. Despite the fact that both zebrafish UEV genes can functionally replace the yeast MMS2 DNA-damage tolerance function, they exhibited differences in DNA-damage response in zebrafish embryos: ablation of DrMms2, but not DrUev1, enhances both spontaneous and DNA-damage induced expression of p53 effectors p21 and mdm2. In addition, DrUbc13 specifically binds Drp53 in an in vitro assay. These observations collectively indicate that zebrafish Mms2 and Ubc13 form a stable complex, which is required for p53-mediated DNA-damage response. (C) 2011 Elsevier B.V. All rights reserved.; The ubiquitin-conjugating enzyme Ubc13 together with a Ubc/E2 variant (Uev) form a stable complex and mediate K63-linked polyubiquitination, which is implicated in DNA damage tolerance in yeast and mammalian cells. The zebrafish Danio rerio is a lower vertebrate model organism widely used in the studies of vertebrate development and environmental stress responses. Here we report the identification and functional characterization of two zebrafish UEV genes, Drmms2 and Druev1. Their deduced amino acid sequences indicate that the two UEV genes evolved separately prior to the appearance of vertebrates. Both zebrafish Uevs form a stable complex with DrUbc13 as well as Ubc13s from yeast and human, and are able to promote Ubc13-mediated K63 polyubiquitination in vitro, suggesting that their biochemical activities are conserved. Despite the fact that both zebrafish UEV genes can functionally replace the yeast MMS2 DNA-damage tolerance function, they exhibited differences in DNA-damage response in zebrafish embryos: ablation of DrMms2, but not DrUev1, enhances both spontaneous and DNA-damage induced expression of p53 effectors p21 and mdm2. In addition, DrUbc13 specifically binds Drp53 in an in vitro assay. These observations collectively indicate that zebrafish Mms2 and Ubc13 form a stable complex, which is required for p53-mediated DNA-damage response. (C) 2011 Elsevier B.V. All rights reserved.
WOS关键词	UBIQUITIN-CONJUGATING-ENZYME ; CELL NUCLEAR ANTIGEN ; NF-KAPPA-B ; POSTREPLICATION REPAIR PATHWAY ; PROTEIN-PROTEIN INTERACTIONS ; SACCHAROMYCES-CEREVISIAE ; IN-VITRO ; SCHIZOSACCHAROMYCES-POMBE ; GENOMIC INSTABILITY ; DEPENDENT KINASE
WOS研究方向	Genetics & Heredity ; Toxicology
语种	英语
WOS记录号	WOS:000301618900008
资助机构	Capital Normal University[10531182313]; Canadian Institutes of Health Research[MOP-93612]; National Natural Science Foundation of China[30871442, 31171390] ; Capital Normal University[10531182313]; Canadian Institutes of Health Research[MOP-93612]; National Natural Science Foundation of China[30871442, 31171390] ; Capital Normal University[10531182313]; Canadian Institutes of Health Research[MOP-93612]; National Natural Science Foundation of China[30871442, 31171390] ; Capital Normal University[10531182313]; Canadian Institutes of Health Research[MOP-93612]; National Natural Science Foundation of China[30871442, 31171390]
公开日期	2012-09-25
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/17023]
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	Cui, ZB (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China.
作者单位	1.Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China 2.Capital Normal Univ, Coll Life Sci, Beijing 100048, Peoples R China 3.Univ Saskatchewan, Dept Microbiol & Immunol, Saskatoon, SK S7N 5E5, Canada
推荐引用方式 GB/T 7714	Wen, Rui,Li, Jie,Xu, Xin,et al. Zebrafish Mms2 promotes K63-linked polyubiquitination and is involved in p53-mediated DNA-damage response[J]. DNA REPAIR,2012,11(2):157-166.
APA	Wen, Rui,Li, Jie,Xu, Xin,Cui, Zongbin,Xiao, Wei,&Cui, ZB .(2012).Zebrafish Mms2 promotes K63-linked polyubiquitination and is involved in p53-mediated DNA-damage response.DNA REPAIR,11(2),157-166.
MLA	Wen, Rui,et al."Zebrafish Mms2 promotes K63-linked polyubiquitination and is involved in p53-mediated DNA-damage response".DNA REPAIR 11.2(2012):157-166.

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