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Bellacosa A , Cicchillitti L , Schepis F , Riccio A , Yeung AT , Matsumoto Y , Golemis EA , Genuardi M , Neri G
MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7) :3969-74
PMID: 10097147 PMCID: PMC22404
AbstractThe DNA mismatch repair (MMR) is a specialized system, highly conserved throughout evolution, involved 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 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 endonuclease activity. Transfection of a MED1 mutant lacking the methyl-CpG-binding domain (MBD) is associated with microsatellite instability (MSI). These findings suggest that MED1 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 human DNA repair.
NotesBellacosa, A Cicchillitti, L Schepis, F Riccio, A Yeung, A T Matsumoto, Y Golemis, E A Genuardi, M Neri, G CA06927/CA/NCI NIH HHS/United States CA78412-01/CA/NCI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3969-74.