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S. cerevisiae Mre11 recruits conjugated SUMO moieties to facilitate the assembly and function of the Mre11-Rad50-Xrs2 complex.
Nucleic Acids Res. 2016 Mar 18; 44(5):2199-213.NA

Abstract

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, Mre11(SIM1) and Mre11(SIM2), which reside on the outermost surface of Mre11. Mre11(SIM1) is indispensable for MRX assembly. Mre11(SIM2) non-covalently links MRX with the SUMO enzymes (E2/Ubc9 and E3/Siz2) to promote global SUMOylation of DNA repair proteins. Mre11(SIM2) acts independently of checkpoint phosphorylation. During meiosis, the mre11(SIM2) mutant, as for mre11S, rad50S and sae2Δ, 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.

Authors+Show Affiliations

Graduate Program of Biotechnology in Medicine, National Tsing Hua University and National Health Research Institutes, Taiwan Institute of Biotechnology, National Tsing Hua University, Hsinchu 300, Taiwan National Institute of Infectious Diseases and Vaccinology, National Health Research Institute, Miaoli 350, Taiwan Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.Graduate Program of Biotechnology in Medicine, National Tsing Hua University and National Health Research Institutes, Taiwan Institute of Biotechnology, National Tsing Hua University, Hsinchu 300, Taiwan.Graduate Program of Biotechnology in Medicine, National Tsing Hua University and National Health Research Institutes, Taiwan National Institute of Infectious Diseases and Vaccinology, National Health Research Institute, Miaoli 350, Taiwan tfwang@gate.sinica.edu.tw.Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan tfwang@gate.sinica.edu.tw.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26743002

Citation

Chen, Yu-Jie, et al. "S. Cerevisiae Mre11 Recruits Conjugated SUMO Moieties to Facilitate the Assembly and Function of the Mre11-Rad50-Xrs2 Complex." Nucleic Acids Research, vol. 44, no. 5, 2016, pp. 2199-213.
Chen YJ, Chuang YC, Chuang CN, et al. S. cerevisiae Mre11 recruits conjugated SUMO moieties to facilitate the assembly and function of the Mre11-Rad50-Xrs2 complex. Nucleic Acids Res. 2016;44(5):2199-213.
Chen, Y. J., Chuang, Y. C., Chuang, C. N., Cheng, Y. H., Chang, C. R., Leng, C. H., & Wang, T. F. (2016). S. cerevisiae Mre11 recruits conjugated SUMO moieties to facilitate the assembly and function of the Mre11-Rad50-Xrs2 complex. Nucleic Acids Research, 44(5), 2199-213. https://doi.org/10.1093/nar/gkv1523
Chen YJ, et al. S. Cerevisiae Mre11 Recruits Conjugated SUMO Moieties to Facilitate the Assembly and Function of the Mre11-Rad50-Xrs2 Complex. Nucleic Acids Res. 2016 Mar 18;44(5):2199-213. PubMed PMID: 26743002.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - S. cerevisiae Mre11 recruits conjugated SUMO moieties to facilitate the assembly and function of the Mre11-Rad50-Xrs2 complex. AU - Chen,Yu-Jie, AU - Chuang,Yu-Chien, AU - Chuang,Chi-Ning, AU - Cheng,Yun-Hsin, AU - Chang,Chuang-Rung, AU - Leng,Chih-Hsiang, AU - Wang,Ting-Fang, Y1 - 2016/01/06/ PY - 2015/12/19/accepted PY - 2015/02/24/received PY - 2016/1/9/entrez PY - 2016/1/9/pubmed PY - 2016/8/9/medline SP - 2199 EP - 213 JF - Nucleic acids research JO - Nucleic Acids Res VL - 44 IS - 5 N2 - 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, Mre11(SIM1) and Mre11(SIM2), which reside on the outermost surface of Mre11. Mre11(SIM1) is indispensable for MRX assembly. Mre11(SIM2) non-covalently links MRX with the SUMO enzymes (E2/Ubc9 and E3/Siz2) to promote global SUMOylation of DNA repair proteins. Mre11(SIM2) acts independently of checkpoint phosphorylation. During meiosis, the mre11(SIM2) mutant, as for mre11S, rad50S and sae2Δ, 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. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/26743002/S__cerevisiae_Mre11_recruits_conjugated_SUMO_moieties_to_facilitate_the_assembly_and_function_of_the_Mre11_Rad50_Xrs2_complex_ L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkv1523 DB - PRIME DP - Unbound Medicine ER -