Progetto Telethon: Identification of ATM binding proteins

Ataxia-telangiectasia (AT) is an autosomal recessive disorder charaeterized by cerebellar ataxia,telangiectases, immune defects, and a predisposition to matignancy. Chromosomal breakage is a feature. At least 4 complemention groups (A, C, D, and E) map to chromosome 11q23 and are Associated with mutations in the ATM gene. The nature of the basic defect is a mystery but is believed to involve one or more of the enzymes concerned with DNA repair or processing. Zakian (1995) provided a dendrogram indicating the relationship between ATM and the various ATM-like genes homologous to the phosphatidylinositol 3-kinase family. She pointed out that'whether or not these ATM-like genes are ATM homologs, continued inquiry in genetically tractable model organisms like yeast and Drosophila will surely provide valuable insight into the functions of this family of proteins’Hawley and friend (1996) commented upon the current state of ATM research and concluded that ATM must play crucial roles in normally developing or undamaged cells, as well as the studied role in irradiated cells, in order to explain the neurologic, immune, and reproductive problems observd in AT patients. They also proposed that ATM may be intimately associated with both p53 and the molecular machinery required for chromosomal exchange, perhaps as componente of the recombination nodules. We are going to investigate on the cellular partners of the ATM protein. Finding these molecules of the molecular mechanisms involved in the pathology of AT, and thus will enable the design of compounds capable of modulating these interactions. The techniques used in this study will be biochemical and molecular, and will allow the identification, purification, and characterization of ATM associated proteins. TT Number: E.0887