MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1

The DNA mismatch repair (MMR) is a specialized system, highly conserved thr oughout evolution, involved in the maintenance of genomic integrity. To ide ntify novel human genes that may function in MMR, we employed the yeast int eraction trap, Using the MMR protein MLH1 as bait, we cloned MED1. The MED1 protein forms a complex with MLH1, binds to methyl-CpG-containing DNA, has homology to bacterial DNA repair glycosylases/lyases, and displays endonuc lease activity, Transfection of a MED1 mutant lacking the methyl-CpG-bindin g domain (MBD) is associated with microsatellite instability (MSI), These f indings suggest that MED1 is a novel human DNA repair protein that may be i nvolved in MMR and, as such, may be a candidate eukaryotic homologue of the bacterial MMR endonuclease, MutH, In addition, these results suggest that cytosine methylation may play a role in human DNA repair.