Telomeric Protein Pin2/TRF1 as an Important ATM Target in

ATM mutations are responsible for the genetic disease ataxia-telangiectasia (A-T). ATM encodes a protein ki-nase that is activated by ionizing radiation-induced double strand DNA breaks. Cells derived from A-T pa-tients show many abnormalities, including accelerated telomere loss and hypersensitivity to ionizing radiation; they enter into mitosis and apoptosis after DNA damage. Pin2 was originally identified as a protein involved in G2/M regulation and is almost identical to TRF1, a telo-meric protein that negatively regulates telomere elon-gation. Pin2 and TRF1, probably encoded by the same gene, PIN2/TRF1, are regulated during the cell cycle. Furthermore, up-regulation of Pin2 or TRF1 induces mitotic entry and apoptosis, a phenotype similar to that of A-T cells after DNA damage. These results sugges