000061673 001__ 61673 000061673 005__ 20230706131402.0 000061673 0247_ $$2doi$$a10.1038/s41598-017-03118-9 000061673 0248_ $$2sideral$$a99636 000061673 037__ $$aART-2017-99636 000061673 041__ $$aeng 000061673 100__ $$aMarcos-Alcalde, Í. 000061673 245__ $$aTwo-step ATP-driven opening of cohesin head 000061673 260__ $$c2017 000061673 5060_ $$aAccess copy available to the general public$$fUnrestricted 000061673 5203_ $$aThe cohesin ring is a protein complex composed of four core subunits: Smc1A, Smc3, Rad21 and Stag1/2. It is involved in chromosome segregation, DNA repair, chromatin organization and transcription regulation. Opening of the ring occurs at the "head" structure, formed of the ATPase domains of Smc1A and Smc3 and Rad21. We investigate the mechanisms of the cohesin ring opening using techniques of free molecular dynamics (MD), steered MD and quantum mechanics/molecular mechanics MD (QM/MM MD). The study allows the thorough analysis of the opening events at the atomic scale: I) ATP hydrolysis at the Smc1A site, evaluating the role of the carboxy-terminal domain of Rad21 in the process; ii) the activation of the Smc3 site potentially mediated by the movement of specific amino acids; and iii) opening of the head domains after the two ATP hydrolysis events. Our study suggests that the cohesin ring opening is triggered by a sequential activation of the ATP sites in which ATP hydrolysis at the Smc1A site induces ATPase activity at the Smc3 site. Our analysis also provides an explanation for the effect of pathogenic variants related to cohesinopathies and cancer. 000061673 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B20$$9info:eu-repo/grantAgreement/ES/FIS/PI15-00707 000061673 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000061673 590__ $$a4.122$$b2017 000061673 591__ $$aMULTIDISCIPLINARY SCIENCES$$b12 / 64 = 0.188$$c2017$$dQ1$$eT1 000061673 592__ $$a1.533$$b2017 000061673 593__ $$aMultidisciplinary$$c2017$$dQ1 000061673 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000061673 700__ $$aMendieta-Moreno, J.I. 000061673 700__ $$0(orcid)0000-0003-0170-7326$$aPuisac, B.$$uUniversidad de Zaragoza 000061673 700__ $$0(orcid)0000-0002-9157-1444$$aGil-Rodríguez, M.C.$$uUniversidad de Zaragoza 000061673 700__ $$0(orcid)0000-0001-8457-1377$$aHernández-Marcos, M. 000061673 700__ $$aSoler-Polo, D. 000061673 700__ $$0(orcid)0000-0002-5732-2209$$aRamos, F.J.$$uUniversidad de Zaragoza 000061673 700__ $$aOrtega, J. 000061673 700__ $$0(orcid)0000-0003-3203-6254$$aPié, J.$$uUniversidad de Zaragoza 000061673 700__ $$aMendieta, J. 000061673 700__ $$aGómez-Puertas, P. 000061673 7102_ $$11005$$2410$$aUniversidad de Zaragoza$$bDpto. Farmacología y Fisiolog.$$cÁrea Fisiología 000061673 7102_ $$11010$$2670$$aUniversidad de Zaragoza$$bDpto. Pediatría Radiol.Med.Fís$$cÁrea Pediatría 000061673 773__ $$g7, 1 (2017), 3266 [14pp.]$$pSci. rep. (Nat. Publ. Group)$$tScientific reports (Nature Publishing Group)$$x2045-2322 000061673 8564_ $$s4821898$$uhttps://zaguan.unizar.es/record/61673/files/texto_completo.pdf$$yVersión publicada 000061673 8564_ $$s113251$$uhttps://zaguan.unizar.es/record/61673/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000061673 909CO $$ooai:zaguan.unizar.es:61673$$particulos$$pdriver 000061673 951__ $$a2023-07-06-12:20:25 000061673 980__ $$aARTICLE