The ends of eukaryotic chromosomes look a lot like double-stranded DNA breaks (DSBs). But DSBs induce checkpoints that stall mitosis during DNA repair, whereas chromosomal ends do not. Unnecessary stalls are thwarted, say Rhett Michelson, Saul Rosenstein, and Ted Weinert (University of Arizona, Tucson, AZ), by telomeric sequences that activate “anticheckpoint” measures.
The authors created extra telomeres in yeast by inducing DSBs next to an internally inserted telomeric repeat. Unlike other DSBs, telomere-adjacent breaks induced only short-lived checkpoint delays. This temporary checkpoint delay probably occurs while telomeric proteins assemble at the new DNA ends—a process that only gets started once telomeric sequences are close to a DNA end. In normal cells, the telomeric proteins are already assembled, so checkpoints never get started.
One simple mechanistic explanation calls for a telomere-bound inhibitor that blocks the activity of Mec1, which initiates the checkpoint response from DSBs. Kinase...
