title: Néstor-Guillermo Progeria Syndrome: a biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation.
abstract: BACKGROUND
  Premature aging syndromes recapitulate many aspects of natural aging and provide an insight into this phenomenon at a molecular and cellular level. The progeria syndromes appear to cause rapid aging through disruption of normal nuclear structure. Recently, a coding mutation (c.34G > A [p.A12T]) in the Barrier to Autointegration Factor 1 (BANF1) gene was identified as the genetic basis of Néstor-Guillermo Progeria syndrome (NGPS). This mutation was described to cause instability in the BANF1 protein, causing a disruption of the nuclear envelope structure.
  
  
  RESULTS
  Here we demonstrate that the BANF1 A12T protein is indeed correctly folded, stable and that the observed phenotype, is likely due to the disruption of the DNA binding surface of the A12T mutant. We demonstrate, using biochemical assays, that the BANF1 A12T protein is impaired in its ability to bind DNA while its interaction with nuclear envelope proteins is unperturbed. Consistent with this, we demonstrate that ectopic expression of the mutant protein induces the NGPS cellular phenotype, while the protein localizes normally to the nuclear envelope.
  
  
  CONCLUSIONS
  Our study clarifies the role of the A12T mutation in NGPS patients, which will be of importance for understanding the development of the disease.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Paquet
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Box
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Ashton
authors.forename: Amila
authors.initials: A
authors.lastname: Suraweera
authors.forename: Laura V
authors.initials: LV
authors.lastname: Croft
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Urquhart
authors.forename: Emma
authors.initials: E
authors.lastname: Bolderson
authors.forename: Shu-Dong
authors.initials: SD
authors.lastname: Zhang
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Byrne
authors.affiliation: School of Biomedical Science, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia. derek.richard@qut.edu.au.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Richard
mesh_terms: D000375:Aging; D000409:Alanine / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation; D011371:Progeria / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D055550:Protein Stability; D013912:Threonine / Q000235:genetics
chemical_list: C501959:BANF1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D013912:Threonine; D004247:DNA; D000409:Alanine