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PMID: 10097147 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 7 ·1999-03-30 ·Pages 3969-74

Bellacosa A, Cicchillitti L, Schepis F, Riccio A, Yeung AT, Matsumoto Y, Golemis EA, Genuardi M, Neri G

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Base Pair Mismatch Base Sequence Carrier Proteins Cell Line Cloning, Molecular DNA Repair Endodeoxyribonucleases/chemistry,isolation & purification,metabolism Humans Kinetics Microsatellite Repeats Molecular Sequence Data MutL Protein Homolog 1 Neoplasm Proteins/isolation & purification,metabolism Nuclear Proteins Oligodeoxyribonucleotides Recombinant Fusion Proteins/biosynthesis Recombinant Proteins/isolation & purification,metabolism Sequence Alignment Sequence Homology, Amino Acid Transfection
Chemicals
Adaptor Proteins, Signal Transducing Carrier Proteins MLH1 protein, human Neoplasm Proteins Nuclear Proteins Oligodeoxyribonucleotides Recombinant Fusion Proteins Recombinant Proteins Endodeoxyribonucleases MBD4 protein, human MutL Protein Homolog 1
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Bellacosa A
Divisions of Population Science, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA. [email protected]
Cicchillitti L
Schepis F
Riccio A
Yeung A T
Matsumoto Y
Golemis E A
Genuardi M
Neri G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.7.3969
Email
[email protected]
Published
1999-03-30
Pages
3969-74
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22404
Subset
IM
Grants
NCI NIH HHS · CA78412-01 · United States
NCI NIH HHS · CA06927 · United States
NCI NIH HHS · R01 CA078412 · United States
NCI NIH HHS · R29 CA078412 · United States
NCI NIH HHS · P30 CA006927 · United States
Databases
GENBANK
AF114784
External Links
PubMed source DOI: 10.1073/pnas.96.7.3969 PMC Full Text View journal details
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