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Mutation research. Fundamental and molecular mechanisms of mutagenesis v.808, 2018년, pp.39 - 47   SCI SCIE
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Drosophila bendless catalyzes K63-linked polyubiquitination and is involved in the response to DNA damage

Bai, Zhiqiang (Beijing Key Laboratory of DNA Damage Responses and College of Life Sciences, Capital Normal University, Beijing 100048, China ) ; Li, Zhouhua (Beijing Key Laboratory of DNA Damage Responses and College of Life Sciences, Capital Normal University, Beijing 100048, China ) ; Xiao, Wei (Beijing Key Laboratory of DNA Damage Responses and College of Life Sciences, Capital Normal University, Beijing 100048, China ) ;
  • 초록  

    Abstract In this study, we report the identification and functional characterization of the Drosophila ben/ubc13 gene, encoding a unique ubiquitin-conjugating enzyme (Ubc or E2), in DNA-damage response. Ben forms a heterodimer with DmUev1a, the only Ubc/E2 variant (Uev) in Drosophila . Ben and DmUev1a act together to catalyze K63-linked polyubiquitination in vitro . ben can functionally rescue the yeast ubc13 null mutant from killing by DNA-damaging agents. We also find that Ben P97S , which was previously described to affect the connectivity between the giant fiber and the tergotrochanter motor neuron, fails to interact with the RING protein Chfr but retains interaction with DmUev1a as well as Uevs from other species. The corresponding yeast Ubc13 P97S interacts with Mms2 but fails to bind Rad5. Consequently, neither ben P97S nor ubc13 P97S is able to complement the yeast ubc13 mutant defective in error-free DNA-damage tolerance. More importantly, the ben P97S mutant flies are more sensitive to a DNA-damaging agent, suggesting that Ben functions in a manner similar to its yeast and mammalian counterparts. Collectively, our observations imply that Ben-DmUev1a-promoted K63-linked polyubiquitination and involvement in DNA-damage response are highly conserved in eukaryotes including flies. Highlights Ben interacts with Uev1a and mediates K63-linked polyubiquitination. Ben is able to functionally complement the yeast ubc13 mutant. The ben 1 mutation is identified and characterized. The budding yeast Ubc13-P97S substitution fails to interact with Rad5 and confer DDT activity. Ben is involved in DNA-damage response in vivo .


  • 주제어

    Drosophila .   Bendless .   Ubc13 .   K63-linked polyubiquitination .   DNA-damage tolerance.  

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