DNA extrusion size determines pathway choice during CAG repeat expansion.

ABSTRACT: DNA triplet repeat expansion causes several primarly neurological disorders like Huntington's disease, myotonic dystrophy type 1, and fragile-X related disorders. There is general consensus that recognition of extrahelical extrusions or hairpin-loop structures (formed by strand slippage) by the DNA mismatch repair protein MutSβ leads to repeat expansion by a mutagenic process. By contrast, the FAN1 nuclease attenuates triplet repeat expansion, the molecular basis of which was explained by our recent finding that FAN1 nuclease cleaves and initiates removal of extrahelical extrusions. Here we show that extrusions containing two or more triplet repeats are subject to recognition and processing by either FAN1 or MutSβ. However, extrusions containing a single triplet escape FAN1 cleavage and ar

SUBMITTER: Bhatia M 

PROVIDER: S-EPMC12721328 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature