title: Cancer predisposing mutations in BRCT domains.
abstract: Members of the breast cancer 1 (BRCA1) carboxy-terminal (BRCT) superfamily are involved in the cellular response to the DNA damage sensing and repair, as well as in the cell cycle control. All proteins are characterized by one or more BRCT domain(s), which provides a flexible framework representing scaffolding element(s) in multi-protein complexes. In particular, BRCA1, nibrin (NBN), and microcephalin (MCPH1), generally considered as molecular models for cancer-prone syndromes, contain BRCT domains able to bind phosphorylated proteins. Mutations within the BRCT domains of BRCA1, NBN, and MCPH1 are responsible for cancer susceptibility, both at the homozygous and heterozygous status. Here, we report a critical analysis of: (i) the BRCT domain structure, (ii) the role of BRCA1, NBN, and MCPH1 in DNA damage sensing and repair as well as in cell cycle control, and (iii) the pathological effects of mutations within the BRCT domains of BRCA1, NBN, and MCPH1.
authors.affiliation: Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, Viale Guglielmo Marconi 446, I-00146 Roma, Italy. dimasi@uniroma3.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: di Masi
authors.forename: Francesca
authors.initials: F
authors.lastname: Gullotta
authors.forename: Valentina
authors.initials: V
authors.lastname: Cappadonna
authors.forename: Loris
authors.initials: L
authors.lastname: Leboffe
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
mesh_terms: D000595:Amino Acid Sequence; D019313:BRCA1 Protein / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D049932:Nijmegen Breakage Syndrome; D017434:Protein Structure, Tertiary
chemical_list: D019313:BRCA1 Protein