Characterization of the Interactome of the Human MutL Homologues MLH1, PMS1, and PMS2

Postreplicative mismatch repair (MMR) involves the concerted action of at least 20 polypeptides. Although the minimal human MMR system has recently been reconstituted in vitro, genetic evidence from different eukaryotic organisms suggests that some steps of the MMR process may be carried out by more...

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Bibliographic Details
Published in:The Journal of biological chemistry 2007-02, Vol.282 (5), p.2976-2986
Main Authors: Cannavo, Elda, Gerrits, Bertran, Marra, Giancarlo, Schlapbach, Ralph, Jiricny, Josef
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Adenosine Triphosphatases - genetics
Adenosine Triphosphatases - metabolism
Animals
Base Pair Mismatch
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Line
DNA Repair Enzymes - genetics
DNA Repair Enzymes - metabolism
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Genetic Vectors
Humans
Methylnitronitrosoguanidine
Mismatch Repair Endonuclease PMS2
MutL Protein Homolog 1
MutL Proteins
Neoplasm Proteins - genetics
Neoplasm Proteins - isolation & purification
Neoplasm Proteins - metabolism
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Recombinant Proteins - metabolism
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Summary:Postreplicative mismatch repair (MMR) involves the concerted action of at least 20 polypeptides. Although the minimal human MMR system has recently been reconstituted in vitro, genetic evidence from different eukaryotic organisms suggests that some steps of the MMR process may be carried out by more than one protein. Moreover, MMR proteins are involved also in other pathways of DNA metabolism, but their exact role in these processes is unknown. In an attempt to gain novel insights into the function of MMR proteins in human cells, we searched for interacting partners of the MutL homologues MLH1 and PMS2 by tandem affinity purification and of PMS1 by large scale immunoprecipitation. In addition to proteins known to interact with the MutL homologues during MMR, mass spectrometric analyses identified a number of other polypeptides, some of which bound to the above proteins with very high affinity. Whereas some of these interactors may represent novel members of the mismatch repairosome, others appear to implicate the MutL homologues in biological processes ranging from intracellular transport through cell signaling to cell morphology, recombination, and ubiquitylation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M609989200