Genome stability control by checkpoint regulation of tRNA gene transcription.

The RNA polymerase III pre-initiation complex (PIC) assembled on yeast tRNA genes naturally causes replication fork pausing that contributes to genome instability. Mechanistic coupling of the fork pausing activity of tRNA genes to replication has long been considered likely, but only recently demonstrated. In contrast to the expectation that this coupling might occur by a passive mechanism such as direct disruption of transcription factor-DNA complexes by a component of the replisome, it turns out that disassembly of the RNA polymerase III PIC is actively controlled by the replication stress checkpoint signal transduction pathway. This advance supports a new model in which checkpoint-dependent disassembly of the transcription machinery at tRNA genes is a vital component of an overall system of genome stability control that also targets replication and DNA repair proteins.