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

A Bellacosa, L Cicchillitti, F Schepis, A Riccio, A Yeung, Y Matsumoto, E Golemis, Maurizio Genuardi, G Neri

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)3969-3974
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
DOIs
Publication statusPublished - 1999

Keywords

  • COLON-CANCER
  • COLORECTAL-CANCER
  • DOMAIN
  • GENE
  • HETERODIMER
  • IDENTIFICATION
  • MUTATOR PHENOTYPE
  • NUCLEAR EXTRACTS
  • PURIFICATION
  • TUMOR-CELLS

Fingerprint

Dive into the research topics of 'MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1'. Together they form a unique fingerprint.

Cite this