Convergent transcription through microsatellite repeat tracts induces cell death.

Microsatellite sequences, composed of short tandem repeats and randomly distributed in human genome, can become unstable during various DNA metabolic processes. Expansions of CAG, GAA, CGG and CCTG repeats located in specific genes are responsible for several human disorders. It is known that a major percentage of human genes simultaneously express both sense and antisense transcripts. Recently, we reported that convergent transcription through a CAG95 tract in human cells leads to cell cycle arrest as well as robust apoptosis. In this study, we studied the effects of convergent transcription through other types of repeats, using cell lines that contain substrates with inducible sense and antisense transcription through CGG66, GAA102, or CCTG134 tracts. We found that convergent transcription through all these repeats inhibits cell growth and induces cell death, though more moderately than convergent transcription through a CAG tract. These results suggest that convergent transcription through various types of tandem repeats represent a novel type of stress to cells.