Zeta MSH-6 Antibody. Zeta’s recombinant rabbit antibody recognizes MSH-6, is a mismatch repair protein that has been implicated in a higher frequency in hereditary nonpolyposis colorectal cancer (HNPCC). Additionally, mutations in MSH-6 are associated with increased risk of colorectal cancer, Lynch syndrome and endometrial cancer, leading to microsatellite instability.
Mismatch repair (MMR) proteins are essential for repairing DNA errors that are generated during DNA replication. There are at least seven MMR proteins in humans, of which four have the most clinical relevance in human cancer biology including MSH-6 (and MLH-1, MSH-2, and PMS-2). These four proteins are arranged as heterodimers in which MLH-1 associates with PMS-2 and MSH-2 associates with MSH-6. The MLH-1/PMS-2 pairing recognizes mismatched nucleotide base pairs and initiates repair, while the MSH-2/MSH-6 pairing acts as an endonuclease (DNA mismatch repair proteins: scientific update and practical guide | Journal of Clinical Pathology (bmj.com)). Many laboratories include MSH-6 along with the other three MMR proteins in their IHC panel in order to assess the expression of these important proteins.
Loss of function of MSH-6 or other MMR proteins results in DMMR (deficient MMR) or impaired DNA repair capability. MSH-6 loss of function results in the accumulation of spontaneous genetic mutations across the genome, affecting the function of many genes which can lead to oncogenic events and leading to an increased risk of development of neoplasia. Identification of MSh-6 loss of function is useful for identifying inherited cancer syndromes and the prediction of response to conventional chemotherapy and immunotherapy.