TY - JOUR
T1 - MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1
AU - Bellacosa, Alfonso
AU - Cicchillitti, Lucia
AU - Schepis, Filippo
AU - Riccio, Antonio
AU - Yeung, Anthony T.
AU - Matsumoto, Yoshihiro
AU - Golemis, Erica A.
AU - Genuardi, Maurizio
AU - Neri, Giovanni
PY - 1999/3/30
Y1 - 1999/3/30
N2 - The 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.
AB - The 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.
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U2 - 10.1073/pnas.96.7.3969
DO - 10.1073/pnas.96.7.3969
M3 - Article
C2 - 10097147
SN - 0027-8424
VL - 96
SP - 3969
EP - 3974
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 7
ER -