FSHD2- and BAMS-associated mutations confer opposing effects on SMCHD1 function

The Journal of Biological Chemistry
Alexandra D GurzauJames M Murphy

Abstract

Structural maintenance of chromosomes flexible hinge domain-containing 1 (Smchd1) plays important roles in epigenetic silencing and normal mammalian development. Recently, heterozygous mutations in SMCHD1 have been reported in two disparate disorders: facioscapulohumeral muscular dystrophy type 2 (FSHD2) and Bosma arhinia microphthalmia syndrome (BAMS). FSHD2-associated mutations lead to loss of function; however, whether BAMS is associated with loss- or gain-of-function mutations in SMCHD1 is unclear. Here, we have assessed the effect of SMCHD1 missense mutations from FSHD2 and BAMS patients on ATP hydrolysis activity and protein conformation and the effect of BAMS mutations on craniofacial development in a Xenopus model. These data demonstrated that FSHD2 mutations only result in decreased ATP hydrolysis, whereas many BAMS mutations can result in elevated ATPase activity and decreased eye size in Xenopus Interestingly, a mutation reported in both an FSHD2 patient and a BAMS patient results in increased ATPase activity and a smaller Xenopus eye size. Mutations in the extended ATPase domain increased catalytic activity, suggesting critical regulatory intramolecular interactions and the possibility of targeting this region thera...Continue Reading

References

Jan 19, 2000·Trends in Biochemical Sciences·R Dutta, M Inouye
Feb 19, 2000·Current Opinion in Structural Biology·L H Pearl, C Prodromou
Jan 28, 2005·American Journal of Human Genetics·Silvère M van der Maarel, Rune R Frants
May 14, 2005·Proceedings of the National Academy of Sciences of the United States of America·Marnie E BlewittEmma Whitelaw
Dec 15, 2005·American Journal of Medical Genetics. Part a·John M Graham, John Lee
Mar 2, 2006·Muscle & Nerve·Rabi Tawil, Silvère M Van Der Maarel
Feb 23, 2008·The Biochemical Journal·Laurence H PearlPaul Workman
Aug 22, 2009·EMBO Reports·Marco RetzlaffJohannes Buchner
Oct 27, 2010·Neurology·J C de GreefR Tawil
Aug 16, 2011·Biochimica Et Biophysica Acta·Chrisostomos Prodromou
Feb 9, 2012·Proceedings of the National Academy of Sciences of the United States of America·Shinji TsutsumiLeonard M Neckers
Mar 2, 2012·European Journal of Human Genetics : EJHG·Andreas LeidenrothJane E Hewitt
Jan 9, 2013·Methods in Molecular Biology·Jeffrey J Babon, James M Murphy
Apr 2, 2013·Nature Structural & Molecular Biology·Ryu-Suke NozawaChikashi Obuse
Oct 1, 2013·American Journal of Human Genetics·Sabrina SacconiSilvère M van der Maarel
Nov 5, 2013·The EMBO Journal·Sevil SofuevaSuzana Hadjur
Dec 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jessica ZuinKerstin S Wendt
May 28, 2014·Human Molecular Genetics·Zizhen YaoStephen J Tapscott
Sep 27, 2014·Human Molecular Genetics·Richard J L F LemmersSilvère M van der Maarel
Nov 6, 2014·European Journal of Human Genetics : EJHG·Mirjam LarsenClemens R Müller
Apr 1, 2012·Journal of Applied Crystallography·Maxim V PetoukhovDmitri I Svergun
Jan 6, 2015·Molecular Cell·Young-Min SohStephan Gruber
May 8, 2015·Nature Protocols·Lawrence A KelleyMichael J E Sternberg
Jun 21, 2015·Proceedings of the National Academy of Sciences of the United States of America·Kelan ChenMarnie E Blewitt
Nov 22, 2015·Current Topics in Developmental Biology·Annita Achilleos, Paul A Trainor
Apr 10, 2016·The Biochemical Journal·Kelan ChenJames M Murphy
Feb 23, 2017·Trends in Genetics : TIG·Natasha JanszMarnie E Blewitt
Jul 12, 2017·Molecular Cell·Marie-Laure Diebold-DurandStephan Gruber
Feb 24, 2018·Science·Mahipal GanjiCees Dekker

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Citations

Jan 31, 2019·Nucleic Acids Research·Camille DionFrédérique Magdinier
Nov 5, 2019·Journal of Medical Genetics·Remko GoossensSilvère M van der Maarel
Feb 23, 2020·Clinical Genetics·Anna GrecoSilvère M van der Maarel
Jul 18, 2019·Communications Biology·Lars C PedersenNatalie D Shaw
Aug 12, 2020·Biochemical Society Transactions·Alexandra D GurzauRichard W Birkinshaw
Mar 19, 2020·Brain : a Journal of Neurology·Carol Dobson-StoneJohn B Kwok
Aug 22, 2018·Nature Structural & Molecular Biology·Natasha JanszMarnie E Blewitt
Apr 25, 2019·Annual Review of Genomics and Human Genetics·Charis L Himeda, Peter L Jones
Jan 12, 2020·Communications Biology·Lars C PedersenNatalie D Shaw
Nov 14, 2020·ELife·Iromi WanigasuriyaMarnie E Blewitt
Jun 11, 2021·The Biochemical Journal·Alexandra D GurzauJames M Murphy

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