Double-Strand Breaks Induce Nuclear-Cytosolic Shuttling of Polymorphic DNA Mismatch Repair Protein MutS Homolog 3 and Binding to NEMO/IKKγ in Colon Cancer Cells.

ABSTRACT:

Background and aims

Human MutS homolog 3 (MSH3) is a DNA mismatch repair protein that recognizes postsynthetic slippage mistakes at microsatellite sequences consisting of dinucleotide or longer repeats in concert with its heterodimer partner MSH2. MSH3 has also been implicated in DNA double-strand break (DSB) repair as part of Homologous Recombination. Loss of MSH3 function is an acquired somatic defect seen in 50% of colorectal cancers and triggered by proinflammatory interleukin-6 signaling, causing a reversible nuclear-to-cytoplasmic shift of the protein. With MSH3's shift to the cytosol, microsatellite frameshift mutations accumulate. Here we examined MSH3 and Δ27bpMSH3, an MSH3 polymorph that alters function of MSH3's nuclear localization signal with enhancement for cytosolic

SUBMITTER: Tseng-Rogenski SS 

PROVIDER: S-EPMC12450631 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature