Mismatch repair (MMR) proteins is a group of nuclear enzymes, which in all proliferating cells participate in repair of base-base mismatch, that occur during DNA replication. Loss of MMR proteins leads to an accumulation of DNA replication errors in the proliferating cells, particularly in areas of the genome with short repetitive nucleotide sequences, a phenomenon known as microsatellite instability (MSI).
The PMS2 protein forms a heterodimer with the MLH1 protein which is then activated in the presence of ATP; this complex coordinates the binding of other proteins that repair DNA errors arising during cell preparation for cell division. The loss of PMS2 expression in tumors can be helpful in identifying hMLH1 mutation carriers and identifies their suitability for mutation analysis. PMS2 gene defects account for a small but significant proportion of colorectal cancers and for a substantial proportion of tumors with microsatellite instability.
Compared to molecular biological techniques, immunohistochemical analysis of MMR protein expression is much simpler and cheaper. Immunohistochemical analysis helps to pinpoint the affected gene and should be readily accessible in a pathology laboratory.
Synthetic peptide corresponding to residues within aa1-100 of PMS2 was used as an immunogen.