Skip Navigation


Nucleic Acids Research Advance Access originally published online on September 13, 2006
Nucleic Acids Research 2006 34(17):4731-4742; doi:10.1093/nar/gkl465
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (1315K) Freely available
Right arrow Screen PDF (1232K) Freely available
Right arrow All Versions of this Article:
34/17/4731    most recent
gkl465v1
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 (12)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Zhong, X.
Right arrow Articles by Kunkel, T. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhong, X.
Right arrow Articles by Kunkel, T. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2006, Vol. 34, No. 17 4731-4742
Published by Oxford University Press 2006

Nucleic Acid Enzymes

The fidelity of DNA synthesis by yeast DNA polymerase zeta alone and with accessory proteins

Xuejun Zhong, Parie Garg2, Carrie M. Stith2, Stephanie A. Nick McElhinny, Grace E. Kissling1, Peter M. J. Burgers2 and Thomas A. Kunkel*

Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS Research Triangle Park, NC 27709, USA 1 Biostatistics Branch, National Institute of Environmental Health Sciences, NIH, DHHS Research Triangle Park, NC 27709, USA 2 Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine St Louis, MO 63110, USA

*To whom correspondence should be addressed at: Bldg 101, Room E342B, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709-2233, USA. Tel: +1 919 541 2644; Fax: +1 919 541 7613; Email: kunkel{at}niehs.nih.gov

Received May 2, 2006. Revised June 15, 2006. Accepted June 15, 2006.

DNA polymerase zeta (pol {zeta}) participates in several DNA transactions in eukaryotic cells that increase spontaneous and damage-induced mutagenesis. To better understand this central role in mutagenesis in vivo, here we report the fidelity of DNA synthesis in vitro by yeast pol {zeta} alone and with RFC, PCNA and RPA. Overall, the accessory proteins have little effect on the fidelity of pol {zeta}. Pol {zeta} is relatively accurate for single base insertion/deletion errors. However, the average base substitution fidelity of pol {zeta} is substantially lower than that of homologous B family pols {alpha}, {delta} and {varepsilon}. Pol {zeta} is particularly error prone for substitutions in specific sequence contexts and generates multiple single base errors clustered in short patches at a rate that is unprecedented in comparison with other polymerases. The unique error specificity of pol {zeta} in vitro is consistent with Pol {zeta}-dependent mutagenic specificity reported in vivo. This fact, combined with the high rate of single base substitution errors and complex mutations observed here, indicates that pol {zeta} contributes to mutagenesis in vivo not only by extending mismatches made by other polymerases, but also by directly generating its own mismatches and then extending them.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors


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
 Nucleic Acids ResHome page
J. E. Stone, G. E. Kissling, S. A. Lujan, I. B. Rogozin, C. M. Stith, P. M. J. Burgers, and T. A. Kunkel
Low-fidelity DNA synthesis by the L979F mutator derivative of Saccharomyces cerevisiae DNA polymerase {zeta}
Nucleic Acids Res., June 1, 2009; 37(11): 3774 - 3787.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Lehner and S. Jinks-Robertson
The mismatch repair system promotes DNA polymerase {zeta}-dependent translesion synthesis in yeast
PNAS, April 7, 2009; 106(14): 5749 - 5754.
[Abstract] [Full Text] [PDF]

Home page
 Microbiol. Mol. Biol. Rev.Home page
L. S. Waters, B. K. Minesinger, M. E. Wiltrout, S. D'Souza, R. V. Woodruff, and G. C. Walker
Eukaryotic Translesion Polymerases and Their Roles and Regulation in DNA Damage Tolerance
Microbiol. Mol. Biol. Rev., March 1, 2009; 73(1): 134 - 154.
[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
M. E. Arana, M. Seki, R. D. Wood, I. B. Rogozin, and T. A. Kunkel
Low-fidelity DNA synthesis by human DNA polymerase theta
Nucleic Acids Res., June 1, 2008; 36(11): 3847 - 3856.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
A. L. Abdulovic, B. K. Minesinger, and S. Jinks-Robertson
The effect of sequence context on spontaneous Pol{zeta}-dependent mutagenesis in Saccharomyces cerevisiae
Nucleic Acids Res., April 1, 2008; 36(6): 2082 - 2093.
[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
A. Wood, P. Garg, and P. M. J. Burgers
A Ubiquitin-binding Motif in the Translesion DNA Polymerase Rev1 Mediates Its Essential Functional Interaction with Ubiquitinated Proliferating Cell Nuclear Antigen in Response to DNA Damage
J. Biol. Chem., July 13, 2007; 282(28): 20256 - 20263.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. A. N. McElhinny, C. M. Stith, P. M. J. Burgers, and T. A. Kunkel
Inefficient Proofreading and Biased Error Rates during Inaccurate DNA Synthesis by a Mutant Derivative of Saccharomyces cerevisiae DNA Polymerase {delta}
J. Biol. Chem., January 26, 2007; 282(4): 2324 - 2332.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. A. Dumstorf, A. B. Clark, Q. Lin, G. E. Kissling, T. Yuan, R. Kucherlapati, W. G. McGregor, and T. A. Kunkel
Participation of mouse DNA polymerase {iota} in strand-biased mutagenic bypass of UV photoproducts and suppression of skin cancer
PNAS, November 28, 2006; 103(48): 18083 - 18088.
[Abstract] [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.