Chromosome fragility at the expanded GAA/TTC tracks depends on repeat orientation and requires mismatch repair system.

ABSTRACT: Expansion of triplex-forming GAA/TTC repeats in the first intron of FRDA gene is known to cause Friedreich’s ataxia. Besides FRDA, there are a number of other highly polymorphic GAA/TTC loci in the human genome where the size variations so far were considered to be a neutral event. Using yeast as a model system, we demonstrate that expanded GAA/TTC repeats represent a threat to eukaryotic genome integrity by triggering double-strand breaks and gross chromosomal rearrangements. The fragility potential strongly depends on the length of the track and orientation of the repeats relative to the replication origin which correlates with their propensity to adopt secondary structure and to block replication progression. We show that fragility is mediated by mismatch repair machinery and requir

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Piotr Mieczkowski 

PROVIDER: E-GEOD-11425 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress