Nse5/6 inhibits the Smc5/6 ATPase and modulates DNA substrate binding.
Détails
Télécharger: Taschner-Nse5-6 inhibits the Smc5-6 ATPase and modulates DNA substrate binding-2021-The EMBO Journal.pdf (9294.40 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_43B3495591E9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Nse5/6 inhibits the Smc5/6 ATPase and modulates DNA substrate binding.
Périodique
The EMBO journal
ISSN
1460-2075 (Electronic)
ISSN-L
0261-4189
Statut éditorial
Publié
Date de publication
02/08/2021
Peer-reviewed
Oui
Volume
40
Numéro
15
Pages
e107807
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
Mots-clé
Adenosine Triphosphate/metabolism, Cell Cycle Proteins/chemistry, Cell Cycle Proteins/genetics, Cell Cycle Proteins/metabolism, Chromosomal Proteins, Non-Histone/chemistry, Chromosomal Proteins, Non-Histone/genetics, Chromosomal Proteins, Non-Histone/metabolism, Cryoelectron Microscopy, Crystallography, X-Ray, DNA, Fungal/metabolism, Hydrolysis, Multiprotein Complexes/chemistry, Multiprotein Complexes/metabolism, Protein Conformation, Saccharomyces cerevisiae/metabolism, Saccharomyces cerevisiae Proteins/chemistry, Saccharomyces cerevisiae Proteins/genetics, Saccharomyces cerevisiae Proteins/metabolism, Smc5/6, chromosome segregation, cohesion, condensin, loop extrusion
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/07/2021 10:08
Dernière modification de la notice
20/07/2022 6:09