description
MSH2:MSH6 (MutSalpha) binds single base mismatches and unpaired loops of 1-2 nucleotides (reviewed in Edelbrock et al. 2013). Human cells contain about 6-fold more MSH2:MSH6 than MSH2:MSH3 (MutSbeta), which mediates repair of larger mismatches, and an imbalance in the ratio can cause a mutator phenotype (Drummond et al. 1997, Marra et al. 1998). The MSH6 subunit is responsible for binding the mismatch, which activates MSH2:MSH6 to exchange ADP for ATP, adopt the conformation to allow movement on the DNA, and interact with downstream effectors PCNA, MLH1:PMS2 and EXO1. The interaction with PCNA initiates excision of the recently replicated strand. MLH1:PMS2 has endonucleolytic activity and makes a nick that is enlarged to a gap of hundreds of nucleotides by EXO1. DNA is polymerized across the gap by DNA polymerase delta and the remaining nick is sealed by DNA ligase I

external resources
NCBI:1270412
REACTOME:R-HSA-5358565
PUBMED:9294177
PUBMED:23391514
PUBMED:9671718

genes
MSH6 , LIG1 , MLH1 , MSH2 , PCNA , PMS2 , POLD1 , POLD2 , RPA1 , RPA2 , RPA3 , EXO1 , POLD3 , POLD4 ,