Cancer Research AACR Conference on Molecular Diagnostics Joint Metastasis Research Society-AACR Conference on Metastasis
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Cell Growth & Differentiation
[Cancer Research 59, 538-541, February 1, 1999]
© 1999 American Association for Cancer Research
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Buermeyer, A. B.
Right arrow Articles by Liskay, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Buermeyer, A. B.
Right arrow Articles by Liskay, R. M.
[Cancer Research 59, 538-541, February 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

The Human MLH1 cDNA Complements DNA Mismatch Repair Defects in Mlh1-deficient Mouse Embryonic Fibroblasts1

Andrew B. Buermeyer, Carmell Wilson-Van Patten, Sean M. Baker and R. Michael Liskay2

Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, Oregon 97201-3098 [A. B. B., C. W-V. P., R. M. L.], and Division of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, California 94720-3104 [S. M. B.]

The DNA mismatch repair gene hMLH1 is reported to function in mutation avoidance, cell cycle checkpoint control, the cytotoxicity of various DNA -damaging agents, and transcription-coupled nucleotide excision repair. Formal proof of the involvement of hMLH1 in these processes requires single gene complementation. We have stably expressed hMLH1 from a transfected cDNA in Mlh1-deficient mouse embryonic fibroblasts. Expression of hMLH1 restored normal levels of mPMS2 protein, reduced spontaneous base substitution and microsatellite mutations, increased sensitivity to the toxic effects of 6-thioguanine (6-TG), and restored 6-TG-induced cell cycle arrest. Our studies confirm that hMLH1 has an essential role in the maintenance of genomic stability and the potentiation of 6-TG cytotoxicity and provide a system for detailed structure/function analysis of the hMLH1 protein.




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
E. Avdievich, C. Reiss, S. J. Scherer, Y. Zhang, S. M. Maier, B. Jin, H. Hou Jr, A. Rosenwald, H. Riedmiller, R. Kucherlapati, et al.
Distinct effects of the recurrent Mlh1G67R mutation on MMR functions, cancer, and meiosis
PNAS, March 18, 2008; 105(11): 4247 - 4252.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
M Candelaria, D Gallardo-Rincon, C Arce, L Cetina, J. Aguilar-Ponce, O Arrieta, A Gonzalez-Fierro, A Chavez-Blanco, E de la Cruz-Hernandez, M. Camargo, et al.
A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors
Ann. Onc., September 1, 2007; 18(9): 1529 - 1538.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. F. Blasi, I. Ventura, G. Aquilina, P. Degan, L. Bertario, C. Bassi, P. Radice, and M. Bignami
A Human Cell-Based Assay to Evaluate the Effects of Alterations in the MLH1 Mismatch Repair Gene.
Cancer Res., September 15, 2006; 66(18): 9036 - 9044.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
V. O'Brien and R. Brown
Signalling cell cycle arrest and cell death through the MMR System
Carcinogenesis, April 1, 2006; 27(4): 682 - 692.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P.-C. Chen, S. Dudley, W. Hagen, D. Dizon, L. Paxton, D. Reichow, S.-R. Yoon, K. Yang, N. Arnheim, R. M. Liskay, et al.
Contributions by MutL Homologues Mlh3 and Pms2 to DNA Mismatch Repair and Tumor Suppression in the Mouse
Cancer Res., October 1, 2005; 65(19): 8662 - 8670.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
J. A. Satia, T. Keku, J. A. Galanko, C. Martin, R. T. Doctolero, A. Tajima, R. S. Sandler, and J. M. Carethers
Diet, Lifestyle, and Genomic Instability in the North Carolina Colon Cancer Study
Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 429 - 436.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Luo, F.-T. Lin, and W.-C. Lin
ATM-Mediated Stabilization of hMutL DNA Mismatch Repair Proteins Augments p53 Activation during DNA Damage
Mol. Cell. Biol., July 15, 2004; 24(14): 6430 - 6444.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
X. Lei, Y. Zhu, A. Tomkinson, and L. Sun
Measurement of DNA mismatch repair activity in live cells
Nucleic Acids Res., July 12, 2004; 32(12): e100 - e100.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Cortellino, D. Turner, V. Masciullo, F. Schepis, D. Albino, R. Daniel, A. M. Skalka, N. J. Meropol, C. Alberti, L. Larue, et al.
From The Cover: The base excision repair enzyme MED1 mediates DNA damage response to antitumor drugs and is associated with mismatch repair system integrity
PNAS, December 9, 2003; 100(25): 15071 - 15076.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
C. T. Warnick, B. Dabbas, S. J. Ilstrup, C. D. Ford, and K. A. Strait
Cell Type-Dependent Regulation of hMLH1 Promoter Activity Is Influenced by the Presence of Multiple Redundant Elements
Mol. Cancer Res., June 1, 2003; 1(8): 610 - 618.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. Tomer, A. B. Buermeyer, M. M. Nguyen, and R. M. Liskay
Contribution of Human Mlh1 and Pms2 ATPase Activities to DNA Mismatch Repair
J. Biol. Chem., June 7, 2002; 277(24): 21801 - 21809.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Lan, Z. Sever-Chroneos, M. W. Strobeck, C.-H. Park, R. Baskaran, W. Edelmann, G. Leone, and E. S. Knudsen
DNA Damage Invokes Mismatch Repair-dependent Cyclin D1 Attenuation and Retinoblastoma Signaling Pathways to Inhibit CDK2
J. Biol. Chem., March 1, 2002; 277(10): 8372 - 8381.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Marra, S. D'Atri, H. Yan, C. Perrera, E. Cannavo', B. Vogelstein, and J. Jiricny
Phenotypic Analysis of hMSH2 Mutations in Mouse Cells Carrying Human Chromosomes
Cancer Res., November 1, 2001; 61(21): 7719 - 7721.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Jacob, M. Aguado, D. Fallik, and F. Praz
The Role of the DNA Mismatch Repair System in the Cytotoxicity of the Topoisomerase Inhibitors Camptothecin and Etoposide to Human Colorectal Cancer Cells
Cancer Res., September 1, 2001; 61(17): 6555 - 6562.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
R. Pepponi, G. Graziani, S. Falcinelli, P. Vernole, L. Levati, P. M. Lacal, E. Pagani, E. Bonmassar, J. Jiricny, and S. D'Atri
hMSH3 overexpression and cellular response to cytotoxic anticancer agents
Carcinogenesis, August 1, 2001; 22(8): 1131 - 1137.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Meyers, M. W. Wagner, H.-S. Hwang, T. J. Kinsella, and D. A. Boothman
Role of the hMLH1 DNA Mismatch Repair Protein in Fluoropyrimidine-mediated Cell Death and Cell Cycle Responses
Cancer Res., July 1, 2001; 61(13): 5193 - 5201.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
P. V. Shcherbakova, M. C. Hall, M. S. Lewis, S. E. Bennett, K. J. Martin, P. R. Bushel, C. A. Afshari, and T. A. Kunkel
Inactivation of DNA Mismatch Repair by Increased Expression of Yeast MLH1
Mol. Cell. Biol., February 1, 2001; 21(3): 940 - 951.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
R. A. Hardman, C. A. Afshari, and J. C. Barrett
Involvement of Mammalian MLH1 in the Apoptotic Response to Peroxide-induced Oxidative Stress
Cancer Res., February 1, 2001; 61(4): 1392 - 1397.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
J. A. Plumb, G. Strathdee, J. Sludden, S. B. Kaye, and R. Brown
Reversal of Drug Resistance in Human Tumor Xenografts by 2'-Deoxy-5-azacytidine-induced Demethylation of the hMLH1 Gene Promoter
Cancer Res., November 1, 2000; 60(21): 6039 - 6044.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
W. K. Leung, J. J. Kim, L. Wu, J. L. Sepulveda, and A. R. Sepulveda
Identification of a Second MutL DNA Mismatch Repair Complex (hPMS1 and hMLH1) in Human Epithelial Cells
J. Biol. Chem., May 19, 2000; 275(21): 15728 - 15732.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Cell Growth & Differentiation
Copyright © 1999 by the American Association for Cancer Research.