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Date publication
septembre 2024
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ANTONY Pierre
,
Dr ROMIER Christophe
,
Dr ENNIFAR Eric
Tous les auteurs :
Vitoria Gomes M, Landwerlin P, Diebold-Durand ML, Shaik TB, Durand A, Troesch E, Weber C, Brillet K, Lemée MV, Decroos C, Dulac L, Antony P, Watrin E, Ennifar E, Golzio C, Romier C
Lien Pubmed
Résumé
Cohesin is key to eukaryotic genome organization and acts throughout the cell cycle in an ATP-dependent manner. The mechanisms underlying cohesin ATPase activity are poorly understood. Here, we characterize distinct steps of the human cohesin ATPase cycle and show that the SMC1A and SMC3 ATPase domains undergo specific but concerted structural rearrangements along this cycle. Specifically, whereas the proximal coiled coil of the SMC1A ATPase domain remains conformationally stable, that of the SMC3 displays an intrinsic flexibility. The ATP-dependent formation of the heterodimeric SMC1A/SMC3 ATPase module (engaged state) favors this flexibility, which is counteracted by NIPBL and DNA binding (clamped state). Opening of the SMC3/RAD21 interface (open-engaged state) stiffens the SMC3 proximal coiled coil, thus constricting together with that of SMC1A the ATPase module DNA-binding chamber. The plasticity of the ATP-dependent interface between the SMC1A and SMC3 ATPase domains enables these structural rearrangements while keeping the ATP gate shut. VIDEO ABSTRACT.
Mots clés
ATP binding, ATPase activity, CP: Molecular biology, Cornelia de Lange syndrome, DNA exit gate, SMC complexes, cohesin, coiled coil, conformational dynamics
Référence
Cell Rep. 2024 09 5;43(9):114656
