Linker domain function predicts pathogenic MLH1 missense variants

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 mech...

Descripción completa

Detalles Bibliográficos
Autores principales: London, James, Martín-López, Juana, Yang, Inho, Liu, Jiaquan, Lee, Jong-Bong, Fishel, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2021
Materias:
Biological Sciences
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936337/
https://www.ncbi.nlm.nih.gov/pubmed/33619096
http://dx.doi.org/10.1073/pnas.2019215118
Descripción
Sumario: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.

Ejemplares similares