000125244 001__ 125244
000125244 005__ 20240111111742.0
000125244 0247_ $$2doi$$a10.1093/pnasnexus/pgac312
000125244 0248_ $$2sideral$$a132921
000125244 037__ $$aART-2022-132921
000125244 041__ $$aeng
000125244 100__ $$aNovo, Nerea$$uUniversidad de Zaragoza
000125244 245__ $$aBeyond a platform protein for the degradosome assembly: the apoptosis-inducing factor as an efficient nuclease involved in chromatinolysis
000125244 260__ $$c2022
000125244 5060_ $$aAccess copy available to the general public$$fUnrestricted
000125244 5203_ $$aThe Apoptosis-Inducing Factor (AIF) is a moonlighting flavoenzyme involved in the assembly of mitochondrial respiratory complexes in healthy cells, but also able to trigger DNA cleavage and parthanatos. Upon apoptotic-stimuli, AIF redistributes from the mitochondria to the nucleus, where upon association with other proteins such as endonuclease CypA and histone H2AX, it is proposed to organize a DNA–degradosome complex. In this work, we provide evidence for the molecular assembly of this complex as well as for the cooperative effects among its protein components to degrade genomic DNA into large fragments. We have also uncovered that AIF has nuclease activity that is stimulated in the presence of either Mg2+ or Ca2+. Such activity allows AIF by itself and in cooperation with CypA to efficiently degrade genomic DNA. Finally, we have identified TopIB and DEK motifs in AIF as responsible for its nuclease activity. These new findings point, for the first time, to AIF as a nuclease able to digest nuclear dsDNA in dying cells, improving our understanding of its role in promoting apoptosis and opening paths for the development of new therapeutic strategies.
000125244 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/E35-20R$$9info:eu-repo/grantAgreement/ES/DGA/LMP27_21$$9info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-103901GB-I00
000125244 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000125244 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000125244 700__ $$aRomero-Tamayo, Silvia
000125244 700__ $$0(orcid)0000-0003-3459-8605$$aMarcuello, Carlos
000125244 700__ $$aBoneta, Sergio$$uUniversidad de Zaragoza
000125244 700__ $$aBlasco-Machin, Irene
000125244 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, Adrián$$uUniversidad de Zaragoza
000125244 700__ $$0(orcid)0000-0001-6676-9478$$aVillanueva, Raquel
000125244 700__ $$0(orcid)0000-0002-6600-1618$$aMoreno-Loshuertos, Raquel$$uUniversidad de Zaragoza
000125244 700__ $$0(orcid)0000-0001-7460-5916$$aLostao, Anabel
000125244 700__ $$0(orcid)0000-0001-8743-0182$$aMedina, Milagros$$uUniversidad de Zaragoza
000125244 700__ $$0(orcid)0000-0003-4076-6118$$aFerreira, Patricia$$uUniversidad de Zaragoza
000125244 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000125244 773__ $$g2, 2 (2022), [11 pp.]$$pPNAS Nexus$$tPNAS Nexus$$x2752-6542
000125244 8564_ $$s3550679$$uhttps://zaguan.unizar.es/record/125244/files/texto_completo.pdf$$yVersión publicada
000125244 8564_ $$s2923218$$uhttps://zaguan.unizar.es/record/125244/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000125244 909CO $$ooai:zaguan.unizar.es:125244$$particulos$$pdriver
000125244 951__ $$a2024-01-11-11:02:14
000125244 980__ $$aARTICLE