Cancer Research The Future of Cancer Research: Science and Patient Impact Cancer Health Disparities Conference 2009
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 Meeting Abstracts Online
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 Yang, J.
Right arrow Articles by Malkas, L. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, J.
Right arrow Articles by Malkas, L. H.
[Cancer Research 64, 5597-5607, August 15, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Altered DNA Polymerase {iota} Expression in Breast Cancer Cells Leads to a Reduction in DNA Replication Fidelity and a Higher Rate of Mutagenesis

Jin Yang, Zhiwen Chen, Yang Liu, Robert J. Hickey and Linda H. Malkas

Department of Medicine, Division of Hematology/Oncology, Cancer Research Institute, Indiana University of School of Medicine, Indianapolis, Indiana

The recently discovered human enzyme DNA polymerase {iota} (pol {iota}) has been shown to have an exceptionally high error rate on artificial DNA templates. Although there is a considerable body of in vitro evidence for a role for pol {iota} in DNA lesion bypass, there is no in vivo evidence to confirm this action. We report here that pol {iota} expression is elevated in breast cancer cells and correlates with a significant decrease in DNA replication fidelity. We also demonstrate that UV treatment of breast cancer cells additionally increases pol {iota} expression with a peak occurring between 30 min and 2 h after cellular insult. This implies that the change in pol {iota} expression is an early event after UV-mediated DNA damage. That pol {iota} may play a role in the higher mutation frequencies observed in breast cancer cells was suggested when a reduction in mutation frequency was found after pol {iota} was immunodepleted from nuclear extracts of the cells. Analysis of the UV-induced mutation spectra revealed that >90% were point mutations. The analysis also demonstrated a decreased C->T nucleotide transition and an increased C->A transversion rate. Overall, our data strongly suggest that pol {iota} may be involved in the generation of both increased spontaneous and translesion mutations during DNA replication in breast cancer cells, thereby contributing to the accumulation of genetic damage.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
Z. Chen, J. Yang, G. Wang, B. Song, J. Li, and Z. Xu
Attenuated Expression of Xeroderma Pigmentosum Group C Is Associated with Critical Events in Human Bladder Cancer Carcinogenesis and Progression
Cancer Res., May 15, 2007; 67(10): 4578 - 4585.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. M. Bacher and P. Schimmel
An editing-defective aminoacyl-tRNA synthetase is mutagenic in aging bacteria via the SOS response
PNAS, February 6, 2007; 104(6): 1907 - 1912.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. H. Malkas, B. S. Herbert, W. Abdel-Aziz, L. E. Dobrolecki, Y. Liu, B. Agarwal, D. Hoelz, S. Badve, L. Schnaper, R. J. Arnold, et al.
A cancer-associated PCNA expressed in breast cancer has implications as a potential biomarker
PNAS, December 19, 2006; 103(51): 19472 - 19477.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. Christmann, M. T. Tomicic, J. Origer, D. Aasland, and B. Kaina
c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF
Nucleic Acids Res., December 2, 2006; 34(22): 6530 - 6539.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. D. Kennedy and A. D. D'Andrea
DNA Repair Pathways in Clinical Practice: Lessons From Pediatric Cancer Susceptibility Syndromes
J. Clin. Oncol., August 10, 2006; 24(23): 3799 - 3808.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J.-Y. Choi and F. P. Guengerich
Kinetic Evidence for Inefficient and Error-prone Bypass across Bulky N2-Guanine DNA Adducts by Human DNA Polymerase {iota}
J. Biol. Chem., May 5, 2006; 281(18): 12315 - 12324.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
X. Lin and S. B. Howell
DNA mismatch repair and p53 function are major determinants of the rate of development of cisplatin resistance
Mol. Cancer Ther., May 1, 2006; 5(5): 1239 - 1247.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Bavoux, A. M. Leopoldino, V. Bergoglio, J. O-Wang, T. Ogi, A. Bieth, J.-G. Judde, S. D. J. Pena, M.-F. Poupon, T. Helleday, et al.
Up-Regulation of the Error-Prone DNA Polymerase {kappa} Promotes Pleiotropic Genetic Alterations and Tumorigenesis
Cancer Res., January 1, 2005; 65(1): 325 - 330.
[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 Meeting Abstracts Online
Copyright © 2004 by the American Association for Cancer Research.