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Zebrafish Ubc13 is required for Lys63-linked polyubiquitination and DNA damage tolerance

文献类型:期刊论文

作者Li, Jie1,3; Wen, Rui2; Andersen, Parkeer2; Liang, Yuping2; Li, Qing1; Xiao, Wei2; Cui, Zongbin1
刊名MOLECULAR AND CELLULAR BIOCHEMISTRY
出版日期2010-10-01
卷号343期号:1-2页码:173-182
关键词Zebrafish Ubiquitin-conjugating enzyme Lys63-linked poly-ubiquitination Protein-protein interaction DNA damage tolerance
ISSN号0300-8177
通讯作者Cui, ZB, Chinese Acad Sci, Inst Hydrobiol, 7 Donghu Rd, Wuhan 430072, Hubei, Peoples R China
中文摘要Ubiquitination is an important post-translational protein modification that functions in diverse cellular processes of all eukaryotic organisms. Conventional Lys48-linked poly-ubiquitination leads to the degradation of specific proteins through 26S proteasomes, while Lys63-linked polyubiquitination appears to regulate protein activities in a non-proteolytic manner. To date, Ubc13 is the only known ubiquitin-conjugating enzyme capable of poly-ubiquitinating target proteins via Lys63-linked chains, and this activity absolutely requires a Ubc variant (Uev or Mms2) as a co-factor. However, Lys63-linked poly-ubiquitination and error-free DNA damage tolerance in zebrafish are yet to be defined. Here, we report molecular cloning and functional characterization of two zebrafish ubc13 genes, ubc13a and ubc13b. Analysis of their genomic structure, nucleotide and protein sequence indicates that the two genes are highly conserved during evolution and derived from whole genome duplication. Zebrafish Ubc13 proteins are able to physically interact with yeast or human Mms2 and both zebrafish ubc13 genes are able to functionally complement the yeast ubc13 null mutant for spontaneous mutagenesis and sensitivity to DNA damaging agents. In addition, upon DNA damage, the expression of zebrafish ubc13a and ubc13b is induced during embryogenesis and zebrafish Ubc13 is associated with nuclear chromatin. These results suggest the involvement of Lys63-linked poly-ubiquitylation in DNA damage response in zebrafish.
英文摘要Ubiquitination is an important post-translational protein modification that functions in diverse cellular processes of all eukaryotic organisms. Conventional Lys48-linked poly-ubiquitination leads to the degradation of specific proteins through 26S proteasomes, while Lys63-linked polyubiquitination appears to regulate protein activities in a non-proteolytic manner. To date, Ubc13 is the only known ubiquitin-conjugating enzyme capable of poly-ubiquitinating target proteins via Lys63-linked chains, and this activity absolutely requires a Ubc variant (Uev or Mms2) as a co-factor. However, Lys63-linked poly-ubiquitination and error-free DNA damage tolerance in zebrafish are yet to be defined. Here, we report molecular cloning and functional characterization of two zebrafish ubc13 genes, ubc13a and ubc13b. Analysis of their genomic structure, nucleotide and protein sequence indicates that the two genes are highly conserved during evolution and derived from whole genome duplication. Zebrafish Ubc13 proteins are able to physically interact with yeast or human Mms2 and both zebrafish ubc13 genes are able to functionally complement the yeast ubc13 null mutant for spontaneous mutagenesis and sensitivity to DNA damaging agents. In addition, upon DNA damage, the expression of zebrafish ubc13a and ubc13b is induced during embryogenesis and zebrafish Ubc13 is associated with nuclear chromatin. These results suggest the involvement of Lys63-linked poly-ubiquitylation in DNA damage response in zebrafish.
WOS标题词Science & Technology ; Life Sciences & Biomedicine
学科主题Cell Biology
类目[WOS]Cell Biology
研究领域[WOS]Cell Biology
关键词[WOS]UBIQUITIN-CONJUGATING-ENZYME ; POSTREPLICATION REPAIR PATHWAY ; DOUBLE-STRAND BREAKS ; SACCHAROMYCES-CEREVISIAE ; PROTEIN-DEGRADATION ; PROMOTING COMPLEX ; HISTONE H2B ; IN-VITRO ; GENE ; YEAST
收录类别SCI
资助信息National Basic Research Program of China [2009CB941200]; Canadian Institutes of Health Research [MOP-53240]
语种英语
WOS记录号WOS:000282050300020
公开日期2010-12-23
源URL[http://ir.ihb.ac.cn/handle/342005/13739]  
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
作者单位1.Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China
2.Univ Saskatchewan, Dept Microbiol & Immunol, Saskatoon, SK S7N 5E5, Canada
3.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
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GB/T 7714
Li, Jie,Wen, Rui,Andersen, Parkeer,et al. Zebrafish Ubc13 is required for Lys63-linked polyubiquitination and DNA damage tolerance[J]. MOLECULAR AND CELLULAR BIOCHEMISTRY,2010,343(1-2):173-182.
APA Li, Jie.,Wen, Rui.,Andersen, Parkeer.,Liang, Yuping.,Li, Qing.,...&Cui, Zongbin.(2010).Zebrafish Ubc13 is required for Lys63-linked polyubiquitination and DNA damage tolerance.MOLECULAR AND CELLULAR BIOCHEMISTRY,343(1-2),173-182.
MLA Li, Jie,et al."Zebrafish Ubc13 is required for Lys63-linked polyubiquitination and DNA damage tolerance".MOLECULAR AND CELLULAR BIOCHEMISTRY 343.1-2(2010):173-182.

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来源:水生生物研究所

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