國家衛生研究院 NHRI:Item 3990099045/9507
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    題名: S. cerevisiae Mre11 recruits conjugated SUMO moieties to facilitate the assembly and function of the Mre11-Rad50-Xrs2 complex
    作者: Chen, YJ;Chuang, YC;Chuang, CN;Cheng, YH;Chang, CR;Leng, CH;Wang, TF
    貢獻者: Division of Vaccine Research and Development
    摘要: Double-strand breaks (DSBs) in chromosomes are the most challenging type of DNA damage. The yeast and mammalian Mre11-Rad50-Xrs2/Nbs1 (MRX/N)-Sae2/Ctp1 complex catalyzes the resection of DSBs induced by secondary structures, chemical adducts or covalently-attached proteins. MRX/N also initiates two parallel DNA damage responses-checkpoint phosphorylation and global SUMOylation-to boost a cell's ability to repair DSBs. However, the molecular mechanism of this SUMO-mediated response is not completely known. In this study, we report that Saccharomyces cerevisiae Mre11 can non-covalently recruit the conjugated SUMO moieties, particularly the poly-SUMO chain. Mre11 has two evolutionarily-conserved SUMO-interacting motifs, Mre11SIM1 and Mre11SIM2, which reside on the outermost surface of Mre11. Mre11SIM1 is indispensable for MRX assembly. Mre11SIM2 non-covalently links MRX with the SUMO enzymes (E2/Ubc9 and E3/Siz2) to promote global SUMOylation of DNA repair proteins. Mre11SIM2 acts independently of checkpoint phosphorylation. During meiosis, the mre11SIM2 mutant, as for mre11S, rad50S and sae2Delta, allows initiation but not processing of Spo11-induced DSBs. Using MRX and DSB repair as a model, our work reveals a general principle in which the conjugated SUMO moieties non-covalently facilitate the assembly and functions of multi-subunit protein complexes.
    日期: 2016-03
    關聯: Nucleic Acids Research. 2016 Mar;44(5):2199-2213.
    Link to: http://dx.doi.org/10.1093/nar/gkv1523
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0305-1048&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000373723100029
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84963828901
    顯示於類別:[冷治湘] 期刊論文

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