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.

MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1 / A. A., Bellacosa; L., Cicchillitti; Schepis, Filippo; A., Riccio; A. T., Yeung; Y., Matsumoto; E. A., Golemis; M., Genuardi; G., Neri. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - STAMPA. - 96:(1999), pp. 3969-3974.

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

SCHEPIS, Filippo;
1999

Abstract

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.
96
3969
3974
MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1 / A. A., Bellacosa; L., Cicchillitti; Schepis, Filippo; A., Riccio; A. T., Yeung; Y., Matsumoto; E. A., Golemis; M., Genuardi; G., Neri. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - STAMPA. - 96:(1999), pp. 3969-3974.
A. A., Bellacosa; L., Cicchillitti; Schepis, Filippo; A., Riccio; A. T., Yeung; Y., Matsumoto; E. A., Golemis; M., Genuardi; G., Neri
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/458474
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