The MSH6 gene located on chromosome 2p16 is one of the mismatch-repair genes involved in hereditary nonpolyposis colorectal cancer (HNPCC). It performs other functions in the cell, like binding to damaged DNA to initiate events that result in damage-induced cytotoxicity. It shares five conserved protein domains (designated I-V) in common with bacterial MutS. However unlike bacterial MutS or Msh2, Msh6 has an additional evolutionarily conserved region preceding domain I, comprised of from 100-more than 600aa, depending on the organism. These N-Terminal Regions (NTRs) of Msh6 contain short, conserved PIP (PCNA interacting protein) boxes near the N-terminus that interact with PCNA, the sliding clamp that participates in both DNA replication and DNA mismatch repair. It forms a heterodimer with MSH2 and is also a part of the BRCA1-associated genome surveillance complex (BASC). The pathological role of Msh6 has also been identified in endometrial cancer.