{"quality_controlled":"1","title":"MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome","status":"public","publisher":"Elsevier","scopus_import":"1","oa":1,"oa_version":"Published Version","date_created":"2020-05-24T22:00:57Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"GaNo"}],"abstract":[{"text":"The NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations inNIPBLaccount for most cases ofthe rare developmental disorder Cornelia de Lange syndrome (CdLS). Here we report aMAU2 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 fornormal cohesin and NIPBL function in cells with a NIPBL early truncating mutation. Despite a predicted fataloutcome of an out-of-frame single nucleotide duplication inNIPBL, engineered in two different cell lines,alternative translation initiation yields a form of NIPBL missing N-terminal residues. This form cannot interactwith 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 protectiveagainst out-of-frame mutations that is potentially relevant for other genetic conditions.","lang":"eng"}],"publication_status":"published","date_published":"2020-05-19T00:00:00Z","issue":"7","month":"05","article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"date_updated":"2023-08-21T06:27:47Z","file":[{"content_type":"application/pdf","file_name":"2020_CellReports_Parenti.pdf","access_level":"open_access","creator":"dernst","relation":"main_file","checksum":"64d8f7467731ee5c166b10b939b8310b","file_id":"7892","date_created":"2020-05-26T11:05:01Z","file_size":4695682,"date_updated":"2020-07-14T12:48:04Z"}],"type":"journal_article","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","day":"19","ddc":["570"],"isi":1,"file_date_updated":"2020-07-14T12:48:04Z","year":"2020","intvolume":"        31","volume":31,"language":[{"iso":"eng"}],"article_number":"107647","_id":"7877","citation":{"mla":"Parenti, Ilaria, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” <i>Cell Reports</i>, vol. 31, no. 7, 107647, Elsevier, 2020, doi:<a href=\"https://doi.org/10.1016/j.celrep.2020.107647\">10.1016/j.celrep.2020.107647</a>.","ieee":"I. Parenti <i>et al.</i>, “MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome,” <i>Cell Reports</i>, vol. 31, no. 7. Elsevier, 2020.","chicago":"Parenti, Ilaria, Farah Diab, Sara Ruiz Gil, Eskeatnaf Mulugeta, Valentina Casa, Riccardo Berutti, Rutger W.W. Brouwer, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” <i>Cell Reports</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.celrep.2020.107647\">https://doi.org/10.1016/j.celrep.2020.107647</a>.","apa":"Parenti, I., Diab, F., Gil, S. R., Mulugeta, E., Casa, V., Berutti, R., … Wendt, K. S. (2020). MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2020.107647\">https://doi.org/10.1016/j.celrep.2020.107647</a>","ista":"Parenti I, Diab F, Gil SR, Mulugeta E, Casa V, Berutti R, Brouwer RWW, Dupé V, Eckhold J, Graf E, Puisac B, Ramos F, Schwarzmayr T, Gines MM, Van Staveren T, Van Ijcken WFJ, Strom TM, Pié J, Watrin E, Kaiser FJ, Wendt KS. 2020. MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. 31(7), 107647.","ama":"Parenti I, Diab F, Gil SR, et al. MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. <i>Cell Reports</i>. 2020;31(7). doi:<a href=\"https://doi.org/10.1016/j.celrep.2020.107647\">10.1016/j.celrep.2020.107647</a>","short":"I. Parenti, F. Diab, S.R. Gil, E. Mulugeta, V. Casa, R. Berutti, R.W.W. Brouwer, V. Dupé, J. Eckhold, E. Graf, B. Puisac, F. Ramos, T. Schwarzmayr, M.M. Gines, T. Van Staveren, W.F.J. Van Ijcken, T.M. Strom, J. Pié, E. Watrin, F.J. Kaiser, K.S. Wendt, Cell Reports 31 (2020)."},"article_type":"original","external_id":{"isi":["000535655200005"]},"publication_identifier":{"eissn":["22111247"]},"doi":"10.1016/j.celrep.2020.107647","publication":"Cell Reports","author":[{"id":"D93538B0-5B71-11E9-AC62-02EBE5697425","full_name":"Parenti, Ilaria","first_name":"Ilaria","last_name":"Parenti"},{"last_name":"Diab","first_name":"Farah","full_name":"Diab, Farah"},{"last_name":"Gil","first_name":"Sara Ruiz","full_name":"Gil, Sara Ruiz"},{"last_name":"Mulugeta","first_name":"Eskeatnaf","full_name":"Mulugeta, Eskeatnaf"},{"full_name":"Casa, Valentina","first_name":"Valentina","last_name":"Casa"},{"first_name":"Riccardo","last_name":"Berutti","full_name":"Berutti, Riccardo"},{"last_name":"Brouwer","first_name":"Rutger W.W.","full_name":"Brouwer, Rutger W.W."},{"full_name":"Dupé, Valerie","first_name":"Valerie","last_name":"Dupé"},{"full_name":"Eckhold, Juliane","last_name":"Eckhold","first_name":"Juliane"},{"last_name":"Graf","first_name":"Elisabeth","full_name":"Graf, Elisabeth"},{"full_name":"Puisac, Beatriz","first_name":"Beatriz","last_name":"Puisac"},{"first_name":"Feliciano","last_name":"Ramos","full_name":"Ramos, Feliciano"},{"last_name":"Schwarzmayr","first_name":"Thomas","full_name":"Schwarzmayr, Thomas"},{"full_name":"Gines, Macarena Moronta","last_name":"Gines","first_name":"Macarena Moronta"},{"full_name":"Van Staveren, Thomas","last_name":"Van Staveren","first_name":"Thomas"},{"last_name":"Van Ijcken","first_name":"Wilfred F.J.","full_name":"Van Ijcken, Wilfred F.J."},{"full_name":"Strom, Tim M.","first_name":"Tim M.","last_name":"Strom"},{"last_name":"Pié","first_name":"Juan","full_name":"Pié, Juan"},{"full_name":"Watrin, Erwan","last_name":"Watrin","first_name":"Erwan"},{"first_name":"Frank J.","last_name":"Kaiser","full_name":"Kaiser, Frank J."},{"full_name":"Wendt, Kerstin S.","last_name":"Wendt","first_name":"Kerstin S."}],"has_accepted_license":"1"}