Structural and Kinetic Analysis of Nucleoside Triphosphate Incorporation Opposite an Abasic Site by Human Translesion DNA Polymerase η
Abstract
The most prevalent lesion in DNA is an abasic site resulting from glycolytic cleavage of a base. In a number of cellular studies, abasic sites preferentially code for dATP insertion (the “A rule”). In some cases frameshifts are also common. X-ray structures with abasic sites in oligonucleotides have been reported for several microbial and human DNA polymerases (pols), e.g. Dpo4, RB69, KlenTaq, yeast pol ι, human (h) pol ι, and human pol β. We reported previously that hpol η is a major pol involved in abasic site bypass (Choi, J.-Y., Lim, S., Kim, E. J., Jo, A., and Guengerich, F. P. (2010 J. Mol. Biol. 404, 34–44). hpol η inserted all four dNTPs in steady-state and pre-steady-state assays, preferentially inserting A and G. In LC-MS analysis of primer-template pairs, A and G were inserted but little C or T was inserted. Frameshifts were observed when an appropriate pyrimidine was positioned 5' to the abasic site in the template. In x-ray structures of hpol η with a non-hydrolyzable analog of dATP or dGTP opposite an abasic site, H-bonding was observed between the phosphate 5' to the abasic site and water H-bonded to N1 and N6 of A and N1 and O6more »
- Authors:
-
- Vanderbilt Univ., Nashville, TN (United States). School of Medicine. Center in Molecular Toxicology. Dept. of Biochemistry
- Publication Date:
- Research Org.:
- Vanderbilt Univ., Nashville, TN (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States)
- OSTI Identifier:
- 1178830
- Grant/Contract Number:
- AC02-06CH11357; R01 ES010375; P01 CA160032; P30 ES000267
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Biological Chemistry
- Additional Journal Information:
- Journal Volume: 290; Journal Issue: 13; Journal ID: ISSN 0021-9258
- Publisher:
- American Society for Biochemistry and Molecular Biology
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; DNA Damage; DNA Polymerase; Enzyme Kinetics; Pre-steady-state Kinetics; X-ray Crystallography
Citation Formats
Patra, Amritaj, Zhang, Qianqian, Lei, Li, Su, Yan, Egli, Martin, and Guengerich, F. Peter. Structural and Kinetic Analysis of Nucleoside Triphosphate Incorporation Opposite an Abasic Site by Human Translesion DNA Polymerase η. United States: N. p., 2015.
Web. doi:10.1074/jbc.M115.637561.
Patra, Amritaj, Zhang, Qianqian, Lei, Li, Su, Yan, Egli, Martin, & Guengerich, F. Peter. Structural and Kinetic Analysis of Nucleoside Triphosphate Incorporation Opposite an Abasic Site by Human Translesion DNA Polymerase η. United States. https://doi.org/10.1074/jbc.M115.637561
Patra, Amritaj, Zhang, Qianqian, Lei, Li, Su, Yan, Egli, Martin, and Guengerich, F. Peter. Mon .
"Structural and Kinetic Analysis of Nucleoside Triphosphate Incorporation Opposite an Abasic Site by Human Translesion DNA Polymerase η". United States. https://doi.org/10.1074/jbc.M115.637561. https://www.osti.gov/servlets/purl/1178830.
@article{osti_1178830,
title = {Structural and Kinetic Analysis of Nucleoside Triphosphate Incorporation Opposite an Abasic Site by Human Translesion DNA Polymerase η},
author = {Patra, Amritaj and Zhang, Qianqian and Lei, Li and Su, Yan and Egli, Martin and Guengerich, F. Peter},
abstractNote = {The most prevalent lesion in DNA is an abasic site resulting from glycolytic cleavage of a base. In a number of cellular studies, abasic sites preferentially code for dATP insertion (the “A rule”). In some cases frameshifts are also common. X-ray structures with abasic sites in oligonucleotides have been reported for several microbial and human DNA polymerases (pols), e.g. Dpo4, RB69, KlenTaq, yeast pol ι, human (h) pol ι, and human pol β. We reported previously that hpol η is a major pol involved in abasic site bypass (Choi, J.-Y., Lim, S., Kim, E. J., Jo, A., and Guengerich, F. P. (2010 J. Mol. Biol. 404, 34–44). hpol η inserted all four dNTPs in steady-state and pre-steady-state assays, preferentially inserting A and G. In LC-MS analysis of primer-template pairs, A and G were inserted but little C or T was inserted. Frameshifts were observed when an appropriate pyrimidine was positioned 5' to the abasic site in the template. In x-ray structures of hpol η with a non-hydrolyzable analog of dATP or dGTP opposite an abasic site, H-bonding was observed between the phosphate 5' to the abasic site and water H-bonded to N1 and N6 of A and N1 and O6 of G nucleoside triphosphate analogs, offering an explanation for what appears to be a “purine rule.” A structure was also obtained for an A inserted and bonded in the primer opposite the abasic site, but it did not pair with a 5' T in the template. Finally, we conclude that hpol η, a major copying enzyme with abasic sites, follows a purine rule, which can also lead to frameshifts. The phenomenon can be explained with H-bonds.},
doi = {10.1074/jbc.M115.637561},
journal = {Journal of Biological Chemistry},
number = 13,
volume = 290,
place = {United States},
year = {Mon Feb 09 00:00:00 EST 2015},
month = {Mon Feb 09 00:00:00 EST 2015}
}
Web of Science
Works referenced in this record:
Replication Past the N 5 -Methyl-Formamidopyrimidine Lesion of Deoxyguanosine by DNA Polymerases and an Improved Procedure for Sequence Analysis of in Vitro Bypass Products by Mass Spectrometry
journal, June 2009
- Christov, Plamen P.; Angel, Karen C.; Guengerich, F. Peter
- Chemical Research in Toxicology, Vol. 22, Issue 6
Specificity of DNA Lesion Bypass by the Yeast DNA Polymerase η
journal, March 2000
- Yuan, Fenghua; Zhang, Yanbin; Rajpal, Deepak K.
- Journal of Biological Chemistry, Vol. 275, Issue 11
Mechanism of Abasic Lesion Bypass Catalyzed by a Y-family DNA Polymerase
journal, January 2007
- Fiala, Kevin A.; Hypes, Cameron D.; Suo, Zucai
- Journal of Biological Chemistry, Vol. 282, Issue 11
Role of DNA polymerase in the bypass of abasic sites in yeast cells
journal, July 2004
- Zhao, B.
- Nucleic Acids Research, Vol. 32, Issue 13
Kinetics, Structure, and Mechanism of 8-Oxo-7,8-dihydro-2′-deoxyguanosine Bypass by Human DNA Polymerase η
journal, April 2014
- Patra, Amritraj; Nagy, Leslie D.; Zhang, Qianqian
- Journal of Biological Chemistry, Vol. 289, Issue 24
Metals, Motifs, and Recognition in the Crystal Structure of a 5S rRNA Domain
journal, November 1997
- Correll, Carl C.; Freeborn, Betty; Moore, Peter B.
- Cell, Vol. 91, Issue 5
The Efficiency and Specificity of Apurinic/Apyrimidinic Site Bypass by Human DNA Polymerase η and Sulfolobus solfataricus Dpo4
journal, September 2003
- Kokoska, Robert J.; McCulloch, Scott D.; Kunkel, Thomas A.
- Journal of Biological Chemistry, Vol. 278, Issue 50
DNA Polymerase β Substrate Specificity: SIDE CHAIN MODULATION OF THE “A-RULE”
journal, September 2009
- Beard, William A.; Shock, David D.; Batra, Vinod K.
- Journal of Biological Chemistry, Vol. 284, Issue 46
Translesion Synthesis across Abasic Lesions by Human B-Family and Y-Family DNA Polymerases α, δ, η, ι, κ, and REV1
journal, November 2010
- Choi, Jeong-Yun; Lim, Seonhee; Kim, Eun-Jin
- Journal of Molecular Biology, Vol. 404, Issue 1
Coot model-building tools for molecular graphics
journal, November 2004
- Emsley, Paul; Cowtan, Kevin
- Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
DNA Synthesis across an Abasic Lesion by Human DNA Polymerase ι
journal, April 2009
- Nair, Deepak T.; Johnson, Robert E.; Prakash, Louise
- Structure, Vol. 17, Issue 4
Structure and mechanism of human DNA polymerase η
journal, June 2010
- Biertümpfel, Christian; Zhao, Ye; Kondo, Yuji
- Nature, Vol. 465, Issue 7301
Replication through an abasic DNA lesion: structural basis for adenine selectivity
journal, April 2010
- Obeid, Samra; Blatter, Nina; Kranaster, Ramon
- The EMBO Journal, Vol. 29, Issue 10
The “A” rule revisited: polymerases as determinants of mutational specificity
journal, February 2002
- Strauss, Bernard S.
- DNA Repair, Vol. 1, Issue 2
The Relative Roles in Vivo of Saccharomyces cerevisiae Pol η, Pol ζ, Rev1 Protein and Pol32 in the Bypass and Mutation Induction of an Abasic Site, T-T (6-4) Photoadduct and T-T cis-syn Cyclobutane Dimer
journal, November 2004
- Gibbs, Peter E. M.; McDonald, John; Woodgate, Roger
- Genetics, Vol. 169, Issue 2
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
Abasic Translesion Synthesis by DNA Polymerase β Violates the “A-rule”: NOVEL TYPES OF NUCLEOTIDE INCORPORATION BY HUMAN DNA POLYMERASE β AT AN ABASIC LESION IN DIFFERENT SEQUENCE CONTEXTS
journal, January 1997
- Efrati, Edna; Tocco, Georges; Eritja, Ramon
- Journal of Biological Chemistry, Vol. 272, Issue 4
Coding properties of poly(deoxycytidylic acid) templates containing uracil or apyrimidinic sites: in vitro modulation of mutagenesis by deoxyribonucleic acid repair enzymes
journal, December 1982
- Boiteux, Serge; Laval, Jacques
- Biochemistry, Vol. 21, Issue 26
Insertion of nucleotides opposite apurinic apyrimidinic sites in deoxyribonucleic acid during in vitro synthesis: uniqueness of adenine nucleotides
journal, September 1983
- Sagher, Daphna; Strauss, Bernard
- Biochemistry, Vol. 22, Issue 19
Caught Bending the A-Rule: Crystal Structures of Translesion DNA Synthesis with a Non-Natural Nucleotide †
journal, September 2007
- Zahn, Karl E.; Belrhali, Hassan; Wallace, Susan S.
- Biochemistry, Vol. 46, Issue 37
Abasic sites from cytosine as termination signals for DNA synthesis
journal, January 1985
- Sagher, Daphna; Strauss, Bernard
- Nucleic Acids Research, Vol. 13, Issue 12
NMRPipe: A multidimensional spectral processing system based on UNIX pipes
journal, November 1995
- Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW.
- Journal of Biomolecular NMR, Vol. 6, Issue 3
Inefficient Bypass of an Abasic Site by DNA Polymerase η
journal, December 2000
- Haracska, Lajos; Washington, M. Todd; Prakash, Satya
- Journal of Biological Chemistry, Vol. 276, Issue 9
Lesion (in)tolerance reveals insights into DNA replication fidelity
journal, April 2004
- Freisinger, Eva; Grollman, Arthur P.; Miller, Holly
- The EMBO Journal, Vol. 23, Issue 7
Steady‐State Kinetic Analysis of DNA Polymerase Single‐Nucleotide Incorporation Products
journal, December 2014
- O'Flaherty, Derek K.; Guengerich, F. Peter
- Current Protocols in Nucleic Acid Chemistry, Vol. 59, Issue 1
Mutagenesis resulting from depurination is an SOS process
journal, November 1982
- Schaaper, Roeland M.; Glickman, Barry W.; Loeb, Lawrence A.
- Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 106, Issue 1
Snapshots of Replication through an Abasic Lesion
journal, March 2004
- Ling, Hong; Boudsocq, François; Woodgate, Roger
- Molecular Cell, Vol. 13, Issue 5
Sparse matrix sampling: a screening method for crystallization of proteins
journal, August 1991
- Jancarik, J.; Kim, S. H.
- Journal of Applied Crystallography, Vol. 24, Issue 4
The CCP4 suite programs for protein crystallography
journal, September 1994
- ,
- Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763
MOLREP an Automated Program for Molecular Replacement
journal, December 1997
- Vagin, A.; Teplyakov, A.
- Journal of Applied Crystallography, Vol. 30, Issue 6, p. 1022-1025
Crystallographic snapshots of a replicative DNA polymerase encountering an abasic site
journal, April 2004
- Hogg, Matthew; Wallace, Susan S.; Doublié, Sylvie
- The EMBO Journal, Vol. 23, Issue 7
UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004
- Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
- Journal of Computational Chemistry, Vol. 25, Issue 13
DNA Synthesis across an Abasic Lesion by Yeast Rev1 DNA Polymerase
journal, February 2011
- Nair, Deepak T.; Johnson, Robert E.; Prakash, Louise
- Journal of Molecular Biology, Vol. 406, Issue 1
Efficient and High Fidelity Incorporation of dCTP Opposite 7,8-Dihydro-8-oxodeoxyguanosine by Sulfolobus solfataricus DNA Polymerase Dpo4
journal, November 2005
- Zang, Hong; Irimia, Adriana; Choi, Jeong-Yun
- Journal of Biological Chemistry, Vol. 281, Issue 4
Explanation of Pre-Steady-State Kinetics and Decreased Burst Amplitude of HIV-1 Reverse Transcriptase at Sites of Modified DNA Bases with an Additional, Nonproductive Enzyme−DNA−Nucleotide Complex †
journal, April 1999
- Furge, Laura Lowe; Guengerich, F. Peter
- Biochemistry, Vol. 38, Issue 15
DNA Adduct Bypass Polymerization by Sulfolobus solfataricus DNA Polymerase Dpo4 : ANALYSIS AND CRYSTAL STRUCTURES OF MULTIPLE BASE PAIR SUBSTITUTION AND FRAMESHIFT PRODUCTS WITH THE ADDUCT 1,
journal, June 2005
- Zang, Hong; Goodenough, Angela K.; Choi, Jeong-Yun
- Journal of Biological Chemistry, Vol. 280, Issue 33
DNA polymerase insertion fidelity. Gel assay for site-specific kinetics.
journal, October 1987
- Boosalis, M. S.; Petruska, J.; Goodman, M. F.
- Journal of Biological Chemistry, Vol. 262, Issue 30
[20] Processing of X-ray diffraction data collected in oscillation mode
book, January 1997
- Otwinowski, Zbyszek; Minor, Wladek
- Macromolecular Crystallography Part A, 307-326
Works referencing / citing this record:
Uncovering a unique approach for damaged DNA replication: A computational investigation of a mutagenic tobacco-derived thymine lesion
journal, January 2019
- Wilson, Katie A.; Holland, Carl D.; Wetmore, Stacey D.
- Nucleic Acids Research, Vol. 47, Issue 4
A non-natural nucleotide uses a specific pocket to selectively inhibit telomerase activity
journal, April 2019
- Hernandez-Sanchez, Wilnelly; Huang, Wei; Plucinsky, Brian
- PLOS Biology, Vol. 17, Issue 4
Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase
journal, May 2019
- Yudkina, Anna V.; Shilkin, Evgeniy S.; Endutkin, Anton V.
- Crystals, Vol. 9, Issue 5
Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells
journal, December 2019
- Moreno, Natália Cestari; de Souza, Tiago Antonio; Garcia, Camila Carrião Machado
- Nucleic Acids Research, Vol. 48, Issue 4
Functions of the major abasic endonuclease (APE1) in cell viability and genotoxin resistance
journal, December 2019
- McNeill, Daniel R.; Whitaker, Amy M.; Stark, Wesley J.
- Mutagenesis, Vol. 35, Issue 1
Mechanism of Ribonucleotide Incorporation by Human DNA Polymerase η
journal, January 2016
- Su, Yan; Egli, Martin; Guengerich, F. Peter
- Journal of Biological Chemistry, Vol. 291, Issue 8
The active site residues Gln55 and Arg73 play a key role in DNA damage bypass by S. cerevisiae Pol η
journal, July 2018
- Boldinova, Elizaveta O.; Ignatov, Artem; Kulbachinskiy, Andrey
- Scientific Reports, Vol. 8, Issue 1
Structural basis of transcriptional stalling and bypass of abasic DNA lesion by RNA polymerase II
journal, February 2018
- Wang, Wei; Walmacq, Celine; Chong, Jenny
- Proceedings of the National Academy of Sciences, Vol. 115, Issue 11
Human DNA polymerase η has reverse transcriptase activity in cellular environments
journal, March 2019
- Su, Yan; Ghodke, Pratibha P.; Egli, Martin
- Journal of Biological Chemistry, Vol. 294, Issue 15