Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (453K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (58)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Zhang, Y.
Right arrow Articles by Wang, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, Y.
Right arrow Articles by Wang, Z.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2000, Vol. 28, No. 21 4147-4156
© 2000 Oxford University Press

Human DNA polymerase {kappa} synthesizes DNA with extraordinarily low fidelity

Yanbin Zhang, Fenghua Yuan, Hua Xin, Xiaohua Wu, Deepak K. Rajpal, Danzhou Yang1 and Zhigang Wang*

Graduate Center for Toxicology and 1Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA

Escherichia coli DNA polymerase IV encoded by the dinB gene is involved in untargeted mutagenesis. Its human homologue is DNA polymerase {kappa} (Pol{kappa}) encoded by the DINB1 gene. Our recent studies have indicated that human Pol{kappa} is capable of both error-free and error-prone translesion DNA synthesis in vitro. However, it is not known whether human Pol{kappa} also plays a role in untargeted mutagenesis. To examine this possibility, we have measured the fidelity of human Pol{kappa} during DNA synthesis from undamaged templates. Using kinetic measurements of nucleotide incorporations and a fidelity assay with gapped M13mp2 DNA, we show that human Pol{kappa} synthesizes DNA with extraordinarily low fidelity. At the lacZ{alpha} target gene, human Pol{kappa} made on average one error for every 200 nucleotides synthesized, with a predominant T->G transversion mutation at a rate of 1/147. The overall error rate of human Pol{kappa} is 1.7-fold lower than human Pol{eta}, but 33-fold higher than human Polß, a DNA polymerase with very low fidelity. Thus, human Pol{kappa} is one of the most inaccurate DNA polymerases known. These results support a role for human Pol{kappa} in untargeted mutagenesis surrounding a DNA lesion and in DNA regions without damage.

* To whom correspondence should be addressed. Tel: +1 859 323 5784; Fax: +1 859 323 1059; Email: zwang@pop.uky.edu


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Immunol.Home page
A. Faili, A. Stary, F. Delbos, S. Weller, S. Aoufouchi, A. Sarasin, J.-C. Weill, and C.-A. Reynaud
A Backup Role of DNA Polymerase {kappa} in Ig Gene Hypermutation Only Takes Place in the Complete Absence of DNA Polymerase {eta}
J. Immunol., May 15, 2009; 182(10): 6353 - 6359.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. M. Sherrer, J. A. Brown, L. R. Pack, V. P. Jasti, J. D. Fowler, A. K. Basu, and Z. Suo
Mechanistic Studies of the Bypass of a Bulky Single-base Lesion Catalyzed by a Y-family DNA Polymerase
J. Biol. Chem., March 6, 2009; 284(10): 6379 - 6388.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
I.-Y. Yang, K. Hashimoto, N. de Wind, I. A. Blair, and M. Moriya
Two Distinct Translesion Synthesis Pathways across a Lipid Peroxidation-derived DNA Adduct in Mammalian Cells
J. Biol. Chem., January 2, 2009; 284(1): 191 - 198.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
L. Jia, N. E. Geacintov, and S. Broyde
The N-clasp of human DNA polymerase {kappa} promotes blockage or error-free bypass of adenine- or guanine-benzo[a]pyrenyl lesions
Nucleic Acids Res., November 1, 2008; 36(20): 6571 - 6584.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
K. Sugasawa
Xeroderma pigmentosum genes: functions inside and outside DNA repair
Carcinogenesis, March 1, 2008; 29(3): 455 - 465.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
S. E. Hile and K. A. Eckert
DNA polymerase kappa produces interrupted mutations and displays polar pausing within mononucleotide microsatellite sequences
Nucleic Acids Res., February 2, 2008; 36(2): 688 - 696.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. A. Fiala, C. D. Hypes, and Z. Suo
Mechanism of Abasic Lesion Bypass Catalyzed by a Y-family DNA Polymerase
J. Biol. Chem., March 16, 2007; 282(11): 8188 - 8198.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
F. Delbos, S. Aoufouchi, A. Faili, J.-C. Weill, and C.-A. Reynaud
DNA polymerase {eta} is the sole contributor of A/T modifications during immunoglobulin gene hypermutation in the mouse
J. Exp. Med., January 22, 2007; 204(1): 17 - 23.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Takenaka, T. Ogi, T. Okada, E. Sonoda, C. Guo, E. C. Friedberg, and S. Takeda
Involvement of Vertebrate Pol{kappa} in Translesion DNA Synthesis across DNA Monoalkylation Damage
J. Biol. Chem., January 27, 2006; 281(4): 2000 - 2004.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
F. Delbos, A. De Smet, A. Faili, S. Aoufouchi, J.-C. Weill, and C.-A. Reynaud
Contribution of DNA polymerase {eta} to immunoglobulin gene hypermutation in the mouse
J. Exp. Med., April 18, 2005; 201(8): 1191 - 1196.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Besaratinia and G. P. Pfeifer
Enhancement of the Mutagenicity of Benzo(a)pyrene Diol Epoxide by a Nonmutagenic Dose of Ultraviolet A Radiation
Cancer Res., December 15, 2003; 63(24): 8708 - 8716.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Kramata, B. Zajc, J. M. Sayer, D. M. Jerina, and C. S.-J. Wei
A Single Site-specific trans-Opened 7,8,9,10-Tetrahydrobenzo[a]pyrene 7,8-Diol 9,10-Epoxide N2-Deoxyguanosine Adduct Induces Mutations at Multiple Sites in DNA
J. Biol. Chem., April 18, 2003; 278(17): 14940 - 14948.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
I.-Y. Yang, H. Miller, Z. Wang, E. G. Frank, H. Ohmori, F. Hanaoka, and M. Moriya
Mammalian Translesion DNA Synthesis across an Acrolein-derived Deoxyguanosine Adduct. PARTICIPATION OF DNA POLYMERASE eta IN ERROR-PRONE SYNTHESIS IN HUMAN CELLS
J. Biol. Chem., April 11, 2003; 278(16): 13989 - 13994.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Okada, E. Sonoda, Y. M. Yamashita, S. Koyoshi, S. Tateishi, M. Yamaizumi, M. Takata, O. Ogawa, and S. Takeda
Involvement of Vertebrate Polkappa in Rad18-independent Postreplication Repair of UV Damage
J. Biol. Chem., December 6, 2002; 277(50): 48690 - 48695.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
W. A. Beard, D. D. Shock, B. J. Vande Berg, and S. H. Wilson
Efficiency of Correct Nucleotide Insertion Governs DNA Polymerase Fidelity
J. Biol. Chem., November 27, 2002; 277(49): 47393 - 47398.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. Rechkoblit, Y. Zhang, D. Guo, Z. Wang, S. Amin, J. Krzeminsky, N. Louneva, and N. E. Geacintov
trans-Lesion Synthesis Past Bulky Benzo[a]pyrene Diol Epoxide N2-dG and N6-dA Lesions Catalyzed by DNA Bypass Polymerases
J. Biol. Chem., August 16, 2002; 277(34): 30488 - 30494.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. Potapova, N. D. F. Grindley, and C. M. Joyce
The Mutational Specificity of the Dbh Lesion Bypass Polymerase and Its Implications
J. Biol. Chem., July 26, 2002; 277(31): 28157 - 28166.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Zhang, X. Wu, F. Yuan, Z. Xie, and Z. Wang
Highly Frequent Frameshift DNA Synthesis by Human DNA Polymerase {micro}
Mol. Cell. Biol., December 1, 2001; 21(23): 7995 - 8006.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Interv.Home page
Z. Wang
DNA DAMAGE-INDUCED MUTAGENESIS : A NOVEL TARGET FOR CANCER PREVENTION
Mol. Interv., December 1, 2001; 1(5): 269 - 281.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
F. Boudsocq, S. Iwai, F. Hanaoka, and R. Woodgate
Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): an archaeal DinB-like DNA polymerase with lesion-bypass properties akin to eukaryotic pol{eta}
Nucleic Acids Res., November 15, 2001; 29(22): 4607 - 4616.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Watanabe, E. Okochi, M. Mochizuki, T. Sugimura, and T. Ushijima
The Presence of Single Nucleotide Instability in Human Breast Cancer Cell Lines
Cancer Res., November 1, 2001; 61(21): 7739 - 7742.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
W. Zhang, P. D. Bardwell, C. J. Woo, V. Poltoratsky, M. D. Scharff, and A. Martin
Clonal instability of V region hypermutation in the Ramos Burkitt's lymphoma cell line
Int. Immunol., September 1, 2001; 13(9): 1175 - 1184.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
X. Wu, D. Guo, F. Yuan, and Z. Wang
Accessibility of DNA polymerases to repair synthesis during nucleotide excision repair in yeast cell-free extracts
Nucleic Acids Res., July 15, 2001; 29(14): 3123 - 3130.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. O-Wang, K. Kawamura, Y. Tada, H. Ohmori, H. Kimura, S. Sakiyama, and M. Tagawa
DNA Polymerase {kappa}, Implicated in Spontaneous and DNA Damage-induced Mutagenesis, Is Overexpressed in Lung Cancer
Cancer Res., July 1, 2001; 61(14): 5366 - 5369.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
Y. Zhang, F. Yuan, X. Wu, J.-S. Taylor, and Z. Wang
Response of human DNA polymerase {{iota}} to DNA lesions
Nucleic Acids Res., February 15, 2001; 29(4): 928 - 935.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Livneh
DNA Damage Control by Novel DNA Polymerases: Translesion Replication and Mutagenesis
J. Biol. Chem., July 6, 2001; 276(28): 25639 - 25642.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.