This event may subsequently lead to recruitment of the MutLa complex and other coordinating factors to proceed with the MMR system. Concurrently, an alternative enzyme may open up the triplex sequence, creating a gap in the nicked opposing strand of DNA, which is filled with additional sequence by a DNA polymerase. Thus, this event may not only resolve the GAA repeat triplex structure, but may at the same time cause further GAA repeat expansions. However, this proposed mechanism does not account for how loss of Pms2 can cause the observed increased magnitude of GAA repeat expansions. Hence, we would suggest that Pms2 can promote GAA repeat contractions by another mechanism. Moreover, this mechanism is only able to explain the potential correlations of GAA repeat expansions, DNA triplex Psychosine from bovine brain structure formation and MMR-error prone activity in the cells with DNA replication ability, hence it is not able to demonstrate the mechanism whereby MMR activity PF-04979064 promotes GAA repeat expansions in non-dividing adult somatic cells. The results of our somatic GAA repeat expansion studies showed that loss of Mlh1 protein leads to stabilization of the expanded GAA repeats in somatic tissues, either due to protection against further GAA repeat expansions or promotion of GAA repeat contractions in neuronal tissues. Despite detecting similar effects of Mlh1 on the dynamics of GAA repeat expansions, we would propose that the Mlh1 mechanism of action may be different between intergenerational transmission and somatic cells. Previous studies have suggested that binding of premature GAA repeat mRNA with the relevant DNA sequence can produce an unusual DNANRNA triplex structure in vitro and in bacteria, which culminates in stalling of RNA polymerase II. Therefore, in the case of post mitotic GAA repeat expansions, a non-canonical R-loop structure might be created during binding of single-stranded template TTC repeat sequences to transcribed GAA mRNA, forming small loop-outs of the single stranded non-template GAA repeats. Evidence shows that these small loop-outs may then be recognized by one of the MutS complexes, subsequently binding with the MutLa complex.