Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT
 
 
DownloadE-Mail
 Lokale TagsFreigabegeschichteDetailsÜbersicht
  Mutations in the MutSalpha interaction interface of MLH1 can abolish DNA mismatch repair

Plotz, G., Welsch, C., Giron-Monzon, L., Friedhoff, P., Albrecht, M., Piiper, A., et al. (2006). Mutations in the MutSalpha interaction interface of MLH1 can abolish DNA mismatch repair. Nucleic Acids Research, 34, 6574-6586.

Item is

 

einblenden: alle ausblenden: alle

Basisdaten

einblenden: ausblenden:
Datensatz-Permalink: https://hdl.handle.net/11858/00-001M-0000-000F-237F-9 Versions-Permalink: https://hdl.handle.net/11858/00-001M-0000-000F-2380-3
Genre: Zeitschriftenartikel

Externe Referenzen

einblenden:

Urheber

einblenden:
ausblenden:
 Urheber:
Plotz, Guido, Autor
Welsch, Christoph1, Autor           
Giron-Monzon, Luis, Autor
Friedhoff, Peter, Autor
Albrecht, Mario1, Autor           
Piiper, Albrecht, Autor
Biondi, Ricardo M.2, Autor
Lengauer, Thomas1, Autor           
Zeuzem, Stefan, Autor
Raedle, Jochen, Autor
Affiliations:
1Computational Biology and Applied Algorithmics, MPI for Informatics, Max Planck Society, ou_40046              
2Max Planck Society, ou_persistent13              

Inhalt

einblenden:
ausblenden:
Schlagwörter: -
 Zusammenfassung: MutL, a heterodimer of MLH1 and PMS2, plays a central role in human DNA mismatch repair. It interacts ATP-dependently with the mismatch detector MutS and assembles and controls further repair enzymes. We tested if the interaction of MutL with DNA-bound MutS is impaired by cancer-associated mutations in MLH1, and identified one mutation (Ala128Pro) which abolished interaction as well as mismatch repair activity. Further examinations revealed three more residues whose mutation interfered with interaction. Homology modelling of MLH1 showed that all residues clustered in a small accessible surface patch, suggesting that the major interaction interface of MutL for MutS is located on the edge of an extensive ß-sheet that backs the MLH1 ATP binding pocket. Bioinformatic analysis confirmed that this patch corresponds to a conserved potential protein– protein interaction interface which is present in both human MLH1 and its E.coli homologue MutL. MutL could be site-specifically crosslinked to MutS from this patch, confirming that the bacterial MutL–MutS complex is established by the corresponding interface in MutL. This is the first study that identifies the conserved major MutL–MutS interaction interface in MLH1 and demonstrates that mutations in this interface can affect interaction and mismatch repair, and thereby can also contribute to cancer development.

Details

einblenden:
ausblenden:
Sprache(n): eng - English
 Datum: 2007-02-212006
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 314628
Anderer: Local-ID: C125673F004B2D7B-BE71BD82A60A15E8C125723700639C8E-Albrecht2006f
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden:

Quelle 1

einblenden:
ausblenden:
Titel: Nucleic Acids Research
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 34 Artikelnummer: - Start- / Endseite: 6574 - 6586 Identifikator: -