PMS1 protein homolog 1 (PMS1)

PMS1 protein homolog 1 is a member of the MutL homolog family and a critical component of the DNA mismatch repair (MMR) pathway, which maintains genomic integrity by correcting base-pair mismatches and insertion-deletion loops during DNA replication [1, 2]. It typically functions as a heterodimer with MLH1, forming the MutL-beta complex [1, 6]. Mutations in the PMS1 gene are linked to hereditary non-polyposis colorectal cancer type 3 (HNPCC3), also known as Lynch syndrome, which predisposes individuals to early-onset colorectal and extra-colonic malignancies [10, 16]. Beyond its role in cancer, PMS1 has recently been identified as a key genetic modifier in Huntington's disease and other triplet repeat expansion disorders [7, 12]. It promotes the somatic expansion of CAG repeats, a process that accelerates disease onset and progression [14]. Consequently, PMS1 is being explored as a therapeutic target; small molecule splice modulators like SKY-0515 and branaplam are designed to reduce PMS1 levels to slow repeat expansion and neurodegeneration [12, 14]. However, therapeutic inhibition of PMS1 must be carefully managed to avoid compromising overall DNA repair capacity and increasing the risk of secondary cancers [14].

Other names

PMS1HNPCC3MLH2PMSL1DNA mismatch repair protein PMS1PMS1 postmeiotic segregation increased 1 (S. cerevisiae)Mismatch repair system componenthMLH2hPMS1

Splice modulation to reduce protein expression via pseudoexon inclusion