PMS2 has both pro-mutagenic and anti-mutagenic effects on repeat instability in the Repeat Expansion Diseases.

ABSTRACT: Expansion of a disease-specific tandem repeat is responsible for >45 Repeat Expansion Diseases (REDs). The mismatch repair protein PMS2 is a modifier of somatic expansion and disease severity in Huntington's disease (HD), a RED resulting from a CAG-repeat expansion. However, PMS2 shows different effects in different RED models, protecting against expansion in some and promoting it in others. To better understand this difference, we carried out a systematic study of the loss of PMS2 in mouse models of HD and the fragile X-related disorders (FXDs), a group of REDs resulting from a CGG-repeat expansion. In both models, loss of one Pms2 allele resulted in more expansions, while loss of both alleles resulted in more expansion in some organs but less in others. Thus, rather than reflecting diffe

SUBMITTER: Jimenez DA 

PROVIDER: S-EPMC11343130 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature