RNA-DNA hybrids promote the expansion of Friedreich's ataxia (GAA)n repeats via break-induced replication.

ABSTRACT: Expansion of simple DNA repeats is responsible for numerous hereditary diseases in humans. The role of DNA replication, repair and transcription in the expansion process has been well documented. Here we analyzed, in a yeast experimental system, the role of RNA-DNA hybrids in genetic instability of long (GAA)n repeats, which cause Friedreich's ataxia. Knocking out both yeast RNase H enzymes, which counteract the formation of RNA-DNA hybrids, increased (GAA)n repeat expansion and contraction rates when the repetitive sequence was transcribed. Unexpectedly, we observed a similar increase in repeat instability in RNase H-deficient cells when we either changed the direction of transcription-replication collisions, or flipped the repeat sequence such that the (UUC)n run occurred in the transcri

SUBMITTER: Neil AJ 

PROVIDER: S-EPMC5909440 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature