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2 août 2021
- doi: 10.15252/embj.2021107807
- issn: 0261-4189
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info:eu-repo/semantics/altIdentifier/doi/10.15252/embj.2021107807
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info:eu-repo/semantics/altIdentifier/pmid/34191293
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info:eu-repo/semantics/altIdentifier/eissn/1460-2075
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_43B3495591E91
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M. Taschner et al., « Nse5/6 inhibits the Smc5/6 ATPase and modulates DNA substrate binding. », Serveur académique Lausannois, ID : 10.15252/embj.2021107807
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Eukaryotic cells employ three SMC (structural maintenance of chromosomes) complexes to control DNA folding and topology. The Smc5/6 complex plays roles in DNA repair and in preventing the accumulation of deleterious DNA junctions. To elucidate how specific features of Smc5/6 govern these functions, we reconstituted the yeast holo-complex. We found that the Nse5/6 sub-complex strongly inhibited the Smc5/6 ATPase by preventing productive ATP binding. This inhibition was relieved by plasmid DNA binding but not by short linear DNA, while opposing effects were observed without Nse5/6. We uncovered two binding sites for Nse5/6 on Smc5/6, based on an Nse5/6 crystal structure and cross-linking mass spectrometry data. One binding site is located at the Smc5/6 arms and one at the heads, the latter likely exerting inhibitory effects on ATP hydrolysis. Cysteine cross-linking demonstrated that the interaction with Nse5/6 anchored the ATPase domains in a non-productive state, which was destabilized by ATP and DNA. Under similar conditions, the Nse4/3/1 module detached from the ATPase. Altogether, we show how DNA substrate selection is modulated by direct inhibition of the Smc5/6 ATPase by Nse5/6.