MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome

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).

Download
OA 2020_CellReports_Parenti.pdf 4.70 MB

Journal Article | Published | English

Scopus indexed
Author
Parenti, IlariaIST Austria; Diab, Farah; Gil, Sara Ruiz; Mulugeta, Eskeatnaf; Casa, Valentina; Berutti, Riccardo; Brouwer, Rutger W.W.; Dupé, Valerie; Eckhold, Juliane; Graf, Elisabeth; Puisac, Beatriz; Ramos, Feliciano
All
Department
Abstract
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.
Publishing Year
Date Published
2020-05-19
Journal Title
Cell Reports
Volume
31
Issue
7
Article Number
107647
eISSN
IST-REx-ID

Cite this

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. Cell Reports. 2020;31(7). doi:10.1016/j.celrep.2020.107647
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. Cell Reports, 31(7). https://doi.org/10.1016/j.celrep.2020.107647
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.” Cell Reports 31, no. 7 (2020). https://doi.org/10.1016/j.celrep.2020.107647.
I. Parenti et al., “MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome,” Cell Reports, vol. 31, no. 7, 2020.
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).
Parenti, Ilaria, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” Cell Reports, vol. 31, no. 7, 107647, Elsevier, 2020, doi:10.1016/j.celrep.2020.107647.
All files available under the following license(s):
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0):
Main File(s)
Access Level
OA Open Access
Date Uploaded
2020-05-26
MD5 Checksum
64d8f7467731ee5c166b10b939b8310b


Export

Marked Publications

Open Data IST Research Explorer

Search this title in

Google Scholar