Check on chromosomal breaks

Common fragile sites are locations on chromosomes that commonly exhibit gaps and breaks and are seen to occur in cells that have been cultured under conditions that partially inhibit DNA replication — such as folate deficiency. These sites are deleted and rearranged in many tumors but are controlled by mechanisms that have remained unclear. In the December 13 Cell, Anne M. Casper and colleagues at the University of Michigan, Ann Arbor, Michigan, USA, show that the cellular checkpoint protein Ataxia-Telangiectasia and Rad3-Related (ATR), but not Ataxia-Telangiectasia Mutated (ATM) regulates fragile site stability (Cell, 111:779–789, December 13, 2002).

Casper et al. used three different techniques to inactivate or disable ATR expression in human cell cultures with deficient ATM from patients with ataxia-telangiectasia. They observed that the replication checkpoint kinase ATR, but not ATM, is critical for maintenance of fragile site stability. ATR deficiency resulted in fragile site expression with and without ...