Investigating the Effects of Missense Mutations in MSH2 Gene Associated with Lynch Syndrome

MSH2-MSH6 is a DNA mismatch repair (MMR) protein complex. 36 mutations in MSH2 have been reported to cause Lynch Syndrome. At the same time, individual genetic testing results suggest that MMR deficiency is associated with breast cancers in some individuals with Lynch Syndrome. Here we demonstrate that the sequence position that have pathogenic mutations in MSH2 protein are highly conserved among species, while the harmless are not. We explore the effects of disease-causing and harmless mutations on the conformational dynamics, stability and binding of MSH2 protein. Our analysis indicates that pathogenic mutations in MSH2 affect protein stability and dynamics and alter binding affinity and flexibility of the protein