Linker domain function predicts pathogenic MLH1 missense variants.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33619096.
- Also identified by DOI 10.1073/pnas.2019215118 and PMC identifier 7936337.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
The pathogenic consequences of 369 unique human HsMLH1 missense variants has been hampered by the lack of a detailed function in mismatch repair (MMR). Here single-molecule images show that HsMSH2-HsMSH6 provides a platform for HsMLH1-HsPMS2 to form a stable sliding clamp on mismatched DNA. The mechanics of sliding clamp progression solves a significant operational puzzle in MMR and provides explicit predictions for the distribution of clinically relevant HsMLH1 missense mutations.
Medical subject headings
- Colorectal Neoplasms, Hereditary Nonpolyposis
- DNA
- DNA Mismatch Repair
- DNA-Binding Proteins
- MutL Protein Homolog 1
- MutS Homolog 2 Protein
- Mutation, Missense