The interplay between hMLH1 and hMRE11: Role in MMR and the effect of hMLH1 mutations

Nianxi Zhao; Fengxue Zhu; Fenghua Yuan; Anoria K Haick; Shinichi Fukushige; Liya Gu; Chengtao Her

doi:10.1016/j.bbrc.2008.03.082

Back

The interplay between hMLH1 and hMRE11: Role in MMR and the effect of hMLH1 mutations

Journal article

Open access

Peer reviewed

The interplay between hMLH1 and hMRE11: Role in MMR and the effect of hMLH1 mutations

Nianxi Zhao, Fengxue Zhu, Fenghua Yuan, Anoria K Haick, Shinichi Fukushige, Liya Gu and Chengtao Her

Biochemical and biophysical research communications, Vol.370(2), pp.338-343

05/30/2008

DOI: https://doi.org/10.1016/j.bbrc.2008.03.082

Handle:

https://hdl.handle.net/2376/107011

PMCID: PMC2443822

PMID: 18373977

Files and links (1)

url

https://doi.org/10.1016/j.bbrc.2008.03.082View

Published (Version of record) Open

Abstract

G2/M checkpoint

hMRE11

MMR

MNU

hMLH1

Cisplatin

Our previous studies indicate that hMRE11 plays a role in MMR, and this function of hMRE11 is most likely mediated by the hMLH1–hMRE11 interaction. Here, we explored the functional implications of the hMLH1–hMRE11 interaction in MMR and the effects of hMLH1 mutations on their interaction. Our in vitro MMR assay demonstrated that the dominant-negative hMRE11452–634 mutant peptide (i.e., harboring only the hMLH1-interacting domain) imparted a significant reduction in both 3′ excision and 3′-directed MMR activities. Furthermore, the expression of hMRE11452–634, and to a lesser extent hMRE111–634 (ATLD1), impaired G2/M checkpoint control in response to MNU and cisplatin treatments, rendering cells resistant to killings by these two anticancer drugs. Analysis of 38 hMLH1 missense mutations showed that the majority of mutations caused significant (>50%) reductions in their interaction with hMRE11, suggesting a potential link between aberrant protein interaction and the pathogenic effects of hMLH1 variants.

Metrics

7 Record Views

Details

Title: The interplay between hMLH1 and hMRE11: Role in MMR and the effect of hMLH1 mutations
Creators: Nianxi Zhao - School of Molecular Biosciences and Center for Reproductive Biology, P.O. Box 644660, Washington State University, Pullman, WA 99164-4660, USA
Fengxue Zhu - School of Molecular Biosciences and Center for Reproductive Biology, P.O. Box 644660, Washington State University, Pullman, WA 99164-4660, USA
Fenghua Yuan - Graduate Center for Toxicology, University of Kentucky Medical Center, Lexington, KY 40536, USA
Anoria K Haick - School of Molecular Biosciences and Center for Reproductive Biology, P.O. Box 644660, Washington State University, Pullman, WA 99164-4660, USA
Shinichi Fukushige - Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Miyagi 980-8575, Japan
Liya Gu - Graduate Center for Toxicology, University of Kentucky Medical Center, Lexington, KY 40536, USA
Chengtao Her - School of Molecular Biosciences and Center for Reproductive Biology, P.O. Box 644660, Washington State University, Pullman, WA 99164-4660, USA
Publication Details: Biochemical and biophysical research communications, Vol.370(2), pp.338-343
Academic Unit: Molecular Biosciences, School of
Publisher: Elsevier Inc
Identifiers: 99900546685701842
Language: English
Resource Type: Journal article