Analysis of the 5' region of PMS2 reveals heterogeneous transcripts and a novel overlapping gene.

The PMS2 gene encodes a protein that is involved in DNA mismatch repair and is mutated in a subset of patients with hereditary nonpolyposis colon cancer (HNPCC). The previously published PMS2 cDNA sequence lacks an upstream in-frame stop codon preceding the presumptive initiating methionine. To evaluate the 5' terminus of the PMS2 coding region further, we isolated additional cDNA clones, RT-PCR products, and the corresponding 5' genomic segment of the PMS2 locus. The PMS2 gene transcripts were found to have heterogeneous but colinear 5' termini, one of which contained an in-frame termination codon preceding the initiating methionine. In addition, a novel gene encoding a 34.5-kDa polypeptide was found to initiate transcriptionally within PMS2 from the opposite strand.