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Cell Rep. 2016 Jul 12;16(2):368-378. doi: 10.1016/j.celrep.2016.06.015. Epub 2016 Jun 30.

Smc5/6 Mediated Sumoylation of the Sgs1-Top3-Rmi1 Complex Promotes Removal of Recombination Intermediates.

Author information

1
Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Programs in Biochemistry, Cell, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
2
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
3
Donnelly Centre and Department of Biochemistry, University of Toronto, Toronto, ON M5S 3E1, Canada.
4
IFOM, The FIRC of Molecular Oncology, Via Adamello 16, 20139, Milan, Italy.
5
Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
6
Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
7
Institute of Biochemistry, Swiss Federal Institute of Technology in Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.
8
Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Programs in Biochemistry, Cell, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA. Electronic address: zhaox1@mskcc.org.

Abstract

Timely removal of DNA recombination intermediates is critical for genome stability. The DNA helicase-topoisomerase complex, Sgs1-Top3-Rmi1 (STR), is the major pathway for processing these intermediates to generate conservative products. However, the mechanisms that promote STR-mediated functions remain to be defined. Here we show that Sgs1 binds to poly-SUMO chains and associates with the Smc5/6 SUMO E3 complex in yeast. Moreover, these interactions contribute to the sumoylation of Sgs1, Top3, and Rmi1 upon the generation of recombination structures. We show that reduced STR sumoylation leads to accumulation of recombination structures, and impaired growth in conditions when these structures arise frequently, highlighting the importance of STR sumoylation. Mechanistically, sumoylation promotes STR inter-subunit interactions and accumulation at DNA repair centers. These findings expand the roles of sumoylation and Smc5/6 in genome maintenance by demonstrating that they foster STR functions in the removal of recombination intermediates.

KEYWORDS:

Sgs1; Smc5/6; protein sumoylation; recombination intermediates

PMID:
27373152
PMCID:
PMC5051638
DOI:
10.1016/j.celrep.2016.06.015
[Indexed for MEDLINE]
Free PMC Article

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