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.
Bibliography
Bellacosa, A., Cicchillitti, L., Schepis, F., Riccio, A., Yeung, A. T., Matsumoto, Y., Golemis, E. A., Genuardi, M., & Neri, G. (1999). MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1. Proceedings of the National Academy of Sciences, 96(7), 3969â3974.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 10:44 a.m.) |
Deposited | 3 years, 2 months ago (June 7, 2022, 12:28 a.m.) |
Indexed | 4 weeks, 2 days ago (Aug. 5, 2025, 8:21 a.m.) |
Issued | 26 years, 5 months ago (March 30, 1999) |
Published | 26 years, 5 months ago (March 30, 1999) |
Published Online | 26 years, 5 months ago (March 30, 1999) |
Published Print | 26 years, 5 months ago (March 30, 1999) |
@article{Bellacosa_1999, title={MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.7.3969}, DOI={10.1073/pnas.96.7.3969}, number={7}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Bellacosa, Alfonso and Cicchillitti, Lucia and Schepis, Filippo and Riccio, Antonio and Yeung, Anthony T. and Matsumoto, Yoshihiro and Golemis, Erica A. and Genuardi, Maurizio and Neri, Giovanni}, year={1999}, month=mar, pages={3969–3974} }