MEDI, a novel human methyl-CPG-binding endonuclease, interacts with DNA mismatch repair protein MLHI

摘要

The DNA mismatch repair (MMR) is a spe- cialized system, highly conserved throughout evolution, in- v0Ivcd in the maintenance of genomic integrity. To identify novel human genes that may function in MMR, we employed the yeast interaction trap. Using the MMR protein MLHI as bait, we cloned MEDI. The MEDI protein forms a complex with MLHI, binds to methyl-CPG-containing DNA, has ho- mology to bacterial DNA repair glycosylases/lyases, and dis- Plays endonuclcase activity. Transfection of a MEDI mutant lacking the methyl-CPG-binding domain (MBD) is associated with microsatellite instability (MSI). These findings suggest that MEDI is a novel human DNA repair protein that may be involved 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 haman DNA repair.