title: Detection of a tandem BRCT in Nbs1 and Xrs2 with functional implications in the DNA damage response.
abstract: BACKGROUND
  Human Nbs1 and its homolog Xrs2 in Saccharomyces cerevisiae are part of the conserved MRN complex (MRX in yeast) which plays a crucial role in maintaining genomic stability. NBS1 corresponds to the gene mutated in the Nijmegen breakage syndrome (NBS) known as a radiation hyper-sensitive disease. Despite the conservation and the importance of the MRN complex, the high sequence divergence between Nbs1 and Xrs2 precluded the identification of common domains downstream of the N-terminal Fork-Head Associated (FHA) domain.
  
  
  RESULTS
  Using HMM-HMM profile comparisons and structure modelling, we assessed the existence of a tandem BRCT in both Nbs1 and Xrs2 after the FHA. The structure-based conservation analysis of the tandem BRCT in Nbs1 supports its function as a phosphoserine binding domain. Remarkably, the 5 bp deletion observed in 95% of NBS patients cleaves the tandem at the linker region while preserving the structural integrity of each BRCT domain in the resulting truncated gene products.
authors.affiliation: Service de Biophysique des Fonctions Membranaires, URA CNRS 2096, Département de Biologie Joliot-Curie, CEA Saclay, 91191 Gif-Sur-Yvette Cedex, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Becker
authors.forename: Vincent
authors.initials: V
authors.lastname: Meyer
authors.forename: Hocine
authors.initials: H
authors.lastname: Madaoui
authors.forename: Raphaël
authors.initials: R
authors.lastname: Guerois
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D004249:DNA Damage; D004260:DNA Repair; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D017434:Protein Structure, Tertiary; D012091:Repetitive Sequences, Nucleic Acid; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C086929:XRS2 protein, S cerevisiae