Chromatin association of the SMC5/6 complex is dependent on binding of its NSE3 subunit to DNA

Zabrady, Katerina, Adamus, Marek, Vondrova, Lucie, Liao, Chunyan, Skoupilova, Hana, Novakova, Marketa, Jurcisinova, Lenka, Alt, Aaron, Oliver, Antony W, Lehmann, Alan R and Palecek, Jan J (2016) Chromatin association of the SMC5/6 complex is dependent on binding of its NSE3 subunit to DNA. Nucleic Acids Research, 44 (3). pp. 1064-1079. ISSN 1362-4962

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SMC5/6 is a highly conserved protein complex related to cohesin and condensin, which are the key components of higher-order chromatin structures. The SMC5/6 complex is essential for proliferation in yeast and is involved in replication fork stability and processing. However, the precise mechanism of action of SMC5/6 is not known. Here we present evidence that the NSE1/NSE3/NSE4 sub-complex of SMC5/6 binds to double-stranded DNA without any preference for DNA-replication/recombination intermediates. Mutations of key basic residues within the NSE1/NSE3/NSE4 DNA-binding surface reduce binding to DNA in vitro. Their introduction into the Schizosaccharomyces pombe genome results in cell death or hypersensitivity to DNA damaging agents. Chromatin immunoprecipitation analysis of the hypomorphic nse3 DNA-binding mutant shows a reduced association of fission yeast SMC5/6 with chromatin. Based on our results, we propose a model for loading of the SMC5/6 complex onto the chromatin.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
Depositing User: Antony Oliver
Date Deposited: 03 Dec 2015 12:01
Last Modified: 07 Mar 2017 00:17

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