The balancing act of DNA repeat expansions

Expansions of microsatellite DNA repeats contribute to the inheritance of nearly 30 developmental and neurological disorders. Significant progress has been made in elucidating the molecular mechanisms of repeat expansions using various model organisms and mammalian cell culture, and models implicating nearly all DNA transactions such as replication, repair, recombination, and transcription have been proposed. It is likely that different models of repeat expansions are not mutually exclusive and may explain repeat instability for different developmental stages and tissues. This review focuses on the contributions from studies in budding yeast toward unraveling the mechanisms and genetic control of repeat expansions, highlighting similarities and differences of replication models and describing a balancing act hypothesis to account for apparent discrepancies.