Repeat expansion in a fragile X model is independent of double strand break repair mediated by Pol θ, RAD52, RAD54 or RAD54B.

ABSTRACT: Microsatellite instability is responsible for the human repeat expansion diseases (REDs). The mutagenic process differs from classical cancer-associated microsatellite instability (MSI) in that it requires the mismatch repair proteins that normally protect against MSI. LIG4, an enzyme essential for non-homologous end-joining (NHEJ), the major pathway for double-strand break repair (DSBR) in mammalian cells, protects against expansion in mouse models. Thus, NHEJ may compete with the expansion pathway for access to a common intermediate. This raises the possibility that expansion involves an NHEJ-independent form of DSBR. Pol θ, a polymerase involved in the theta-mediated end joining (TMEJ) DSBR pathway, has been proposed to play a role in repeat expansion. Here we examine the effect of the

SUBMITTER: Hayward BE 

PROVIDER: S-EPMC11814403 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature