000089914 001__ 89914
000089914 005__ 20230706131406.0
000089914 0247_ $$2doi$$a10.1016/j.celrep.2020.107647
000089914 0248_ $$2sideral$$a118153
000089914 037__ $$aART-2020-118153
000089914 041__ $$aeng
000089914 100__ $$aParenti, I.
000089914 245__ $$aMAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome
000089914 260__ $$c2020
000089914 5060_ $$aAccess copy available to the general public$$fUnrestricted
000089914 5203_ $$aThe NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations in NIPBL account for most cases of the rare developmental disorder Cornelia de Lange syndrome (CdLS). Here we report a MAU2 variant causing CdLS, a deletion of seven amino acids that impairs the interaction between MAU2 and the NIPBL N terminus. Investigating this interaction, we discovered that MAU2 and the NIPBL N terminus are largely dispensable for normal cohesin and NIPBL function in cells with a NIPBL early truncating mutation. Despite a predicted fatal outcome of an out-of-frame single nucleotide duplication in NIPBL, engineered in two different cell lines, alternative translation initiation yields a form of NIPBL missing N-terminal residues. This form cannot interact with MAU2, but binds DNA and mediates cohesin loading. Altogether, our work reveals that cohesin loading can occur independently of functional NIPBL/MAU2 complexes and highlights a novel mechanism protective against out-of-frame mutations that is potentially relevant for other genetic conditions.
000089914 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000089914 590__ $$a9.423$$b2020
000089914 591__ $$aCELL BIOLOGY$$b33 / 195 = 0.169$$c2020$$dQ1$$eT1
000089914 592__ $$a6.264$$b2020
000089914 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2020$$dQ1
000089914 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000089914 700__ $$aDiab, F.
000089914 700__ $$aGil, S.R.
000089914 700__ $$aMulugeta, E.
000089914 700__ $$aCasa, V.
000089914 700__ $$aBerutti, R.
000089914 700__ $$aBrouwer, R.W.W.
000089914 700__ $$aDupé, V.
000089914 700__ $$aEckhold, J.
000089914 700__ $$aGraf, E.
000089914 700__ $$0(orcid)0000-0003-0170-7326$$aPuisac, B.$$uUniversidad de Zaragoza
000089914 700__ $$0(orcid)0000-0002-5732-2209$$aRamos, F.$$uUniversidad de Zaragoza
000089914 700__ $$aSchwarzmayr, T.
000089914 700__ $$aGines, M.M.
000089914 700__ $$avan Staveren, T.
000089914 700__ $$avan IJcken, W.F.J.
000089914 700__ $$aStrom, T.M.
000089914 700__ $$0(orcid)0000-0003-3203-6254$$aPié, J.$$uUniversidad de Zaragoza
000089914 700__ $$aWatrin, E.
000089914 700__ $$aKaiser, F.J.
000089914 700__ $$aWendt, K.S.
000089914 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000089914 7102_ $$11011$$2670$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Pediatría
000089914 773__ $$g31, 7 (2020), 107647 [22 pp]$$pCell Reports$$tCell Reports$$x2211-1247
000089914 8564_ $$s3072608$$uhttps://zaguan.unizar.es/record/89914/files/texto_completo.pdf$$yVersión publicada
000089914 8564_ $$s35776$$uhttps://zaguan.unizar.es/record/89914/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000089914 909CO $$ooai:zaguan.unizar.es:89914$$particulos$$pdriver
000089914 951__ $$a2023-07-06-12:20:40
000089914 980__ $$aARTICLE