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Author, Editor(s)
Author(s):
Plotz, Guido
Welsch, Christoph
Giron-Monzon, Luis
Friedhoff, Peter
Albrecht, Mario
Piiper, Albrecht
Biondi, Ricardo M.
Lengauer, Thomas
Zeuzem, Stefan
Raedle, Jochen		dblp
dblp
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dblp
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Not MPG Author(s):
Plotz, Guido
Welsch, Christoph
Giron-Monzon, Luis
Friedhoff, Peter
Piiper, Albrecht
Biondi Ricardo M.
Zeuzem, Stefan
Raedle, Jochen

BibTeX cite key*:

Albrecht2006f

Title

Title*:

Mutations in the MutSalpha interaction interface of MLH1 can abolish DNA mismatch repair


Plotz.pdf (4583.04 KB)

Journal

Journal Title*:

Nucleic Acids Research
Journal's URL:


Download URL
for the article:

http://dx.doi.org/10.1093/nar/gkl944
Language:

English

Publisher

Publisher's
Name:

Oxford University Press
Publisher's URL:


Publisher's
Address:

Oxford, UK
ISSN:

0305-1048

Vol, No, pp, Date

Volume*:

34
Number:

22

Publishing Date:

2006

Pages*:

6574-6586
Number of
VG Pages:


Page Start:


Page End:


Sequence Number:


DOI:

10.1093/nar/gkl944

Note, Abstract, ©

Note:


(LaTeX) Abstract:

MutL{alpha}, a heterodimer of MLH1 and PMS2, plays a central role in human DNA mismatch repair. It interacts ATP-dependently with the mismatch detector MutS{alpha} and assembles and controls further repair enzymes. We tested if the interaction of MutL{alpha} with DNA-bound MutS{alpha} 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{alpha} for MutS{alpha} 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{alpha}–MutS{alpha} 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.

URL for the Abstract:

http://nar.oxfordjournals.org/cgi/content/abstract/34/22/6574

Categories,
Keywords:


HyperLinks / References / URLs:


Copyright Message:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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BibTeX Entry:

@ARTICLE{Albrecht2006f,
AUTHOR = {Plotz, Guido and Welsch, Christoph and Giron-Monzon, Luis and Friedhoff, Peter and Albrecht, Mario and Piiper, Albrecht and Biondi, Ricardo M. and Lengauer, Thomas and Zeuzem, Stefan and Raedle, Jochen},
 TITLE = {Mutations in the {MutSalpha} interaction interface of {MLH1} can abolish {DNA} mismatch repair},
 JOURNAL = {Nucleic Acids Research},
 PUBLISHER = {Oxford University Press},
 YEAR = {2006},
 NUMBER = {22},
 VOLUME = {34},
 PAGES = {6574--6586},
 ADDRESS = {Oxford, UK},
 ISBN = {0305-1048},
 DOI = {10.1093/nar/gkl944},
}

Entry last modified by Anja Becker, 02/14/2008
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Editor(s)
Mario Albrecht		Created
12/01/2006 07:08:01 PM
Revisions
6.
5.
4.
3.
2.		Editor(s)
Anja Becker
Anja Becker
Uwe Brahm
Christine Kiesel
Christine Kiesel		Edit Dates
14.02.2008 14:11:15
14.02.2008 14:09:23
2007-07-11 12:31:22
21.02.2007 10:29:37
12/26/2006 07:51:12 PM
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