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学科主题: Cell Biology
题名: Zebrafish Ubc13 is required for Lys63-linked polyubiquitination and DNA damage tolerance
作者: Li, Jie1, 3; Wen, Rui2; Andersen, Parkeer2; Liang, Yuping2; Li, Qing1; Xiao, Wei2; Cui, Zongbin1
通讯作者: Cui, ZB, Chinese Acad Sci, Inst Hydrobiol, 7 Donghu Rd, Wuhan 430072, Hubei, Peoples R China
关键词: Zebrafish ; Ubiquitin-conjugating enzyme ; Lys63-linked poly-ubiquitination ; Protein-protein interaction ; DNA damage tolerance
刊名: MOLECULAR AND CELLULAR BIOCHEMISTRY
发表日期: 2010-10-01
DOI: 10.1007/s11010-010-0511-9
卷: 343, 期:1-2, 页:173-182
收录类别: SCI
文章类型: Article
部门归属: [Li, Jie; Li, Qing; Cui, Zongbin] Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China; [Wen, Rui; Andersen, Parkeer; Liang, Yuping; Xiao, Wei] Univ Saskatchewan, Dept Microbiol & Immunol, Saskatoon, SK S7N 5E5, Canada; [Li, Jie] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: National Basic Research Program of China [2009CB941200]; Canadian Institutes of Health Research [MOP-53240]
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
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.
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
语种: 英语
WOS记录号: WOS:000282050300020
ISSN号: 0300-8177
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/13739
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.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

Recommended Citation:
Li, Jie; Wen, Rui; Andersen, Parkeer; Liang, Yuping; Li, Qing; Xiao, Wei; Cui, Zongbin.Zebrafish Ubc13 is required for Lys63-linked polyubiquitination and DNA damage tolerance,MOLECULAR AND CELLULAR BIOCHEMISTRY,2010,343(1-2):173-182
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