ABSTRACT
Defects in the gene Ataxia Telangiectasia Mutated (ATM) are responsible for the development of ataxia telangiectasia (AT), an incurable cancer-prone disease that is accompanied by a pleiotropic set of conditions including, amongst others, neurological and immuno logical deficiencies. ATM is a large protein kinase that controls numerous cellular processes, particu larly those involved with maintaining chromosome stability. In recent years, a wealth o f data have shown that ATM regulates multiple events throughout the cell cycle, including replication origin firing, telomere dysfunction and programmed events at antigen receptor loci in T-and B-cells of lymphoid origin. As all of these processes utilize DNA-double stranded break (DSB) intermediates, ATM suppresses the generation of DSB-inducing translocation events through regulating multiple pathways. Here, we discuss the activation and role of ATM kinase and its closely associated factors in maintaining chromosomal stability in various DSB signaling pathways. Notably, we highlight some recent advances suggesting that ATM suppresses chromosomal translocations in lymphoid cells through its role in maintaining free DNA ends during DNA end joining, a process that links DSB repair, chromatin function and, the development of lymphoma.
