Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair
Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair
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DOI：
10.1016/s0092-8674(00)80575-9
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发表时间：
1999-03-05
期刊：
影响因子：
64.5
通讯作者：
Pickart, CM
中科院分区：
文献类型：
--
作者：
Hofmann, RM;Pickart, CM
泛素结合酶变异体(UEV)蛋白类似于泛素结合酶(E2s)，但缺乏确定的E2活性部位残基。MMS2编码的UEV蛋白在遗传上与酿酒酵母复制后无错误的DNA修复有关。我们发现Mms2p与UBC13编码的E2形成了一个特定的异构体复合体，并且是依赖Ubc13p通过赖氨酸63连接的多泛素链组装所必需的。UBC13酵母菌株对紫外线敏感，UBC13、MMS2和泛素(UbiK63R)基因的单、双和三个突变体表现出类似的表型。这些发现支持一个模型，在该模型中，Ms2p/Ubc13p复合体组装了新的多泛素链，用于DNA修复信号，并表明UEV蛋白可能在泛素结合中增加多样性和选择性。
Ubiquitin-conjugating enzyme variant (UEV) proteins resemble ubiquitin-conjugating enzymes (E2s) but lack the defining E2 active-site residue. The MMS2-encoded UEV protein has been genetically implicated in error-free postreplicative DNA repair in Saccharomyces cerevisiae. We show that Mms2p forms a specific heteromeric complex with the UBC13-encoded E2 and is required for the Ubc13p-dependent assembly of polyubiquitin chains linked through lysine 63. A ubc13 yeast strain is UV sensitive, and single, double, and triple mutants of the UBC13, MMS2, and ubiquitin (ubiK63R) genes display a comparable phenotype. These findings support a model in which an Mms2p/Ubc13p complex assembles novel polyubiquitin chains for signaling in DNA repair, and they suggest that UEV proteins may act to increase diversity and selectivity in ubiquitin conjugation.