Human DNA polymerase θ grasps the primer terminus to mediate DNA repair

Zahn, Karl E.; Averill, April M.; Aller, Pierre; Wood, Richard D.; Doublié, Sylvie

doi:10.1038/nsmb.2993

Title: Human DNA polymerase θ grasps the primer terminus to mediate DNA repair

Journal Article · Mon Mar 16 00:00:00 EDT 2015 · Nature Structural & Molecular Biology

DOI:https://doi.org/10.1038/nsmb.2993· OSTI ID:1197030

Zahn, Karl E. ^[1]; Averill, April M. ^[1]; Aller, Pierre ^[2]; Wood, Richard D. ^[3]; Doublié, Sylvie ^[1]

Univ. of Vermont, Burlington, VT (United States). Dept. of Microbiology and Molecular Genetics
Diamond Light Source, Didcot (United Kingdom)
Univ. of Texas MD Anderson Cancer Center, Smithville, TX (United States). Dept. of Epigenetics & Molecular Carcinogenesis

DNA polymerase θ protects against genomic instability via an alternative end-joining repair pathway for DNA double-strand breaks. Polymerase θ is overexpressed in breast, lung and oral cancers, and reduction of its activity in mammalian cells increases sensitivity to double-strand break–inducing agents, including ionizing radiation. Reported in this paper are crystal structures of the C-terminal polymerase domain from human polymerase θ, illustrating two potential modes of dimerization. One structure depicts insertion of ddATP opposite an abasic-site analog during translesion DNA synthesis. The second structure describes a cognate ddGTP complex. Polymerase θ uses a specialized thumb subdomain to establish unique upstream contacts to the primer DNA strand, including an interaction with the 3'-terminal phosphate from one of five distinctive insertion loops. Finally, these observations demonstrate how polymerase θ grasps the primer to bypass DNA lesions or extend poorly annealed DNA termini to mediate end-joining.

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Research Organization:: Univ. of Vermont, Burlington, VT (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Inst. of Health (NIH) (United States); Cancer Prevention and Research Inst. of Texas (United States)

Contributing Organization:: Diamond Light Source, Didcot (United Kingdom); Univ. of Texas MD Anderson Cancer Center, Smithville, TX (United States)

Grant/Contract Number:: AC02-06CH11357; R01 CA052040; CA097175; RP130297; ACB-12002; AGM-12006

OSTI ID:: 1197030

Journal Information:: Nature Structural & Molecular Biology, Vol. 22, Issue 4; ISSN 1545-9993

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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References (61)

A Role for DNA Polymerase θ in Promoting Replication through Oxidative DNA Lesion, Thymine Glycol, in Human Cells Yoon, Jung-Hoon; Roy Choudhury, Jayati; Park, Jeseong Journal of Biological Chemistry, Vol. 289, Issue 19 https://doi.org/10.1074/jbc.M114.556977	journal	March 2014
Solving structures of protein complexes by molecular replacement with Phaser McCoy, Airlie J. Acta Crystallographica Section D Biological Crystallography, Vol. 63, Issue 1 https://doi.org/10.1107/S0907444906045975	journal	December 2006
Quantifying the energetic contributions of desolvation and π-electron density during translesion DNA synthesis Motea, Edward A.; Lee, Irene; Berdis, Anthony J. Nucleic Acids Research, Vol. 39, Issue 4 https://doi.org/10.1093/nar/gkq925	journal	October 2010
Human DNA polymerase possesses 5'-dRP lyase activity and functions in single-nucleotide base excision repair in vitro Prasad, R.; Longley, M. J.; Sharief, F. S. Nucleic Acids Research, Vol. 37, Issue 6 https://doi.org/10.1093/nar/gkp035	journal	January 2009
Polymerase theta-mediated end joining of replication-associated DNA breaks in C. elegans Roerink, S. F.; van Schendel, R.; Tijsterman, M. Genome Research, Vol. 24, Issue 6 https://doi.org/10.1101/gr.170431.113	journal	March 2014
Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 Å resolution Doublié, Sylvie; Tabor, Stanley; Long, Alexander M. Nature, Vol. 391, Issue 6664 https://doi.org/10.1038/34593	journal	January 1998
Vertebrate POLQ and POLβ Cooperate in Base Excision Repair of Oxidative DNA Damage Jun, Nakamura,; Hiroshi, Arakawa,; Akira, Yasui, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/623z-fw19	text	January 2006
Evolutionary conservation of residues in vertebrate DNA polymerase N conferring low fidelity and bypass activity Takata, Kei-ichi; Arana, Mercedes E.; Seki, Mineaki Nucleic Acids Research, Vol. 38, Issue 10 https://doi.org/10.1093/nar/gkq048	journal	February 2010
DNA polymerase up-regulation is associated with poor survival in breast cancer, perturbs DNA replication, and promotes genetic instability Lemee, F.; Bergoglio, V.; Fernandez-Vidal, A. Proceedings of the National Academy of Sciences, Vol. 107, Issue 30 https://doi.org/10.1073/pnas.0910759107	journal	July 2010
Reevaluation of the role of DNA polymerase θ in somatic hypermutation of immunoglobulin genes Martomo, Stella A.; Saribasak, Huseyin; Yokoi, Masayuki DNA Repair, Vol. 7, Issue 9 https://doi.org/10.1016/j.dnarep.2008.04.002	journal	September 2008
DNA polymerase θ (POLQ) can extend from mismatches and from bases opposite a (6-4) photoproduct Seki, Mineaki; Wood, Richard D. DNA Repair, Vol. 7, Issue 1 https://doi.org/10.1016/j.dnarep.2007.08.005	journal	January 2008
Mechanism of Suppression of Chromosomal Instability by DNA Polymerase POLQ Kei-ichi, Takata,; C., Hensley, Sean; O., Bylund, Göran The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/jp4t-2957	text	January 2014
Structure-based design of Taq DNA polymerases with improved properties of dideoxynucleotide incorporation Li, Y.; Mitaxov, V.; Waksman, G. Proceedings of the National Academy of Sciences, Vol. 96, Issue 17 https://doi.org/10.1073/pnas.96.17.9491	journal	August 1999
Human DNA Polymerase N (POLN) Is a Low Fidelity Enzyme Capable of Error-free Bypass of 5 S -Thymine Glycol Takata, Kei-ichi; Shimizu, Tatsuhiko; Iwai, Shigenori Journal of Biological Chemistry, Vol. 281, Issue 33 https://doi.org/10.1074/jbc.m604317200	journal	June 2006
Synthesis-dependent microhomology-mediated end joining accounts for multiple types of repair junctions Yu, Amy Marie; McVey, Mitch Nucleic Acids Research, Vol. 38, Issue 17 https://doi.org/10.1093/nar/gkq379	journal	May 2010
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
Identification of upregulated genes in oral squamous cell carcinomas Lessa, Roberta C.; Campos, Antonio Hugo J. F. M.; de Freitas, Carlos Elias Head & Neck https://doi.org/10.1002/hed.23169	journal	January 2012
High-efficiency bypass of DNA damage by human DNA polymerase Q Seki, Mineaki; Masutani, Chikahide; Yang, Lee Wei The EMBO Journal, Vol. 23, Issue 22 https://doi.org/10.1038/sj.emboj.7600424	journal	October 2004
Mechanism of microhomology-mediated end-joining promoted by human DNA polymerase θ Kent, Tatiana; Chandramouly, Gurushankar; McDevitt, Shane Michael Nature Structural & Molecular Biology, Vol. 22, Issue 3 https://doi.org/10.1038/nsmb.2961	journal	February 2015
Mechanism of Suppression of Chromosomal Instability by DNA Polymerase POLQ Yousefzadeh, Matthew J.; Wyatt, David W.; Takata, Kei-ichi PLoS Genetics, Vol. 10, Issue 10 https://doi.org/10.1371/journal.pgen.1004654	journal	October 2014
Use of knowledge-based restraints in phenix.refine to improve macromolecular refinement at low resolution Headd, Jeffrey J.; Echols, Nathaniel; Afonine, Pavel V. Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4 https://doi.org/10.1107/S0907444911047834	journal	March 2012
POLN, a Nuclear PolA Family DNA Polymerase Homologous to the DNA Cross-link Sensitivity Protein Mus308 Marini, Federica; Kim, Nayun; Schuffert, Anthony Journal of Biological Chemistry, Vol. 278, Issue 34 https://doi.org/10.1074/jbc.m305646200	journal	June 2003
The Phenix software for automated determination of macromolecular structures Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Methods, Vol. 55, Issue 1 https://doi.org/10.1016/j.ymeth.2011.07.005	journal	September 2011
The Structure of a High Fidelity DNA Polymerase Bound to a Mismatched Nucleotide Reveals an “Ajar” Intermediate Conformation in the Nucleotide Selection Mechanism Wu, Eugene Y.; Beese, Lorena S. Journal of Biological Chemistry, Vol. 286, Issue 22 https://doi.org/10.1074/jbc.M110.191130	journal	March 2011
Identification of 5'-deoxyribose phosphate lyase activity in human DNA polymerase and its role in mitochondrial base excision repair in vitro Longley, M. J.; Prasad, R.; Srivastava, D. K. Proceedings of the National Academy of Sciences, Vol. 95, Issue 21 https://doi.org/10.1073/pnas.95.21.12244	journal	October 1998
Low-fidelity DNA synthesis by human DNA polymerase theta Arana, M. E.; Seki, M.; Wood, R. D. Nucleic Acids Research, Vol. 36, Issue 11 https://doi.org/10.1093/nar/gkn310	journal	May 2008
Structure of DNA polymerase I Klenow fragment bound to duplex DNA Beese, L.; Derbyshire, V.; Steitz, T. Science, Vol. 260, Issue 5106 https://doi.org/10.1126/science.8469987	journal	April 1993
Caught Bending the A-Rule: Crystal Structures of Translesion DNA Synthesis with a Non-Natural Nucleotide ^† Zahn, Karl E.; Belrhali, Hassan; Wallace, Susan S. Biochemistry, Vol. 46, Issue 37 https://doi.org/10.1021/bi7008807	journal	September 2007
Nucleic acid polymerases use a general acid for nucleotidyl transfer Castro, Christian; Smidansky, Eric D.; Arnold, Jamie J. Nature Structural & Molecular Biology, Vol. 16, Issue 2 https://doi.org/10.1038/nsmb.1540	journal	January 2009
Promiscuous DNA synthesis by human DNA polymerase θ Hogg, Matthew; Sauer-Eriksson, A. Elisabeth; Johansson, Erik Nucleic Acids Research, Vol. 40, Issue 6 https://doi.org/10.1093/nar/gkr1102	journal	November 2011
DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes Santarpia, Libero; Iwamoto, Takayuki; Di Leo, Angelo The Oncologist, Vol. 18, Issue 10 https://doi.org/10.1634/theoncologist.2013-0163	journal	September 2013
A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites Koole, Wouter; van Schendel, Robin; Karambelas, Andrea E. Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms4216	journal	February 2014
Amino Acid Templating Mechanisms in Selection of Nucleotides Opposite Abasic Sites by a Family A DNA Polymerase Obeid, Samra; Welte, Wolfram; Diederichs, Kay Journal of Biological Chemistry, Vol. 287, Issue 17 https://doi.org/10.1074/jbc.M111.334904	journal	February 2012
Lesion Bypass Activity of DNA Polymerase θ (POLQ) Is an Intrinsic Property of the Pol Domain and Depends on Unique Sequence Inserts Hogg, Matthew; Seki, Mineaki; Wood, Richard D. Journal of Molecular Biology, Vol. 405, Issue 3 https://doi.org/10.1016/j.jmb.2010.10.041	journal	January 2011
Statistical density modification with non-crystallographic symmetry Terwilliger, Thomas C. Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 12 https://doi.org/10.1107/S0907444902016360	journal	November 2002
The Retrohoming of Linear Group II Intron RNAs in Drosophila melanogaster Occurs by Both DNA Ligase 4–Dependent and –Independent Mechanisms White, Travis B.; Lambowitz, Alan M. PLoS Genetics, Vol. 8, Issue 2 https://doi.org/10.1371/journal.pgen.1002534	journal	February 2012
DNA polymerase POLQ and cellular defense against DNA damage Yousefzadeh, Matthew J.; Wood, Richard D. DNA Repair, Vol. 12, Issue 1 https://doi.org/10.1016/j.dnarep.2012.10.004	journal	January 2013
Lack of DNA Polymerase θ (POLQ) Radiosensitizes Bone Marrow Stromal Cells In Vitro and Increases Reticulocyte Micronuclei after Total-Body Irradiation Goff, Julie P.; Shields, Donna S.; Seki, Mineaki Radiation Research, Vol. 172, Issue 2 https://doi.org/10.1667/RR1598.1	journal	August 2009
Vertebrate POLQ and POLβ Cooperate in Base Excision Repair of Oxidative DNA Damage Yoshimura, Michio; Kohzaki, Masaoki; Nakamura, Jun Molecular Cell, Vol. 24, Issue 1 https://doi.org/10.1016/j.molcel.2006.07.032	journal	October 2006
Molecular cloning of Drosophila mus308, a gene involved in DNA cross-link repair with homology to prokaryotic DNA polymerase I genes. Harris, P. V.; Mazina, O. M.; Leonhardt, E. A. Molecular and Cellular Biology, Vol. 16, Issue 10 https://doi.org/10.1128/MCB.16.10.5764	journal	October 1996
Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair Ceccaldi, Raphael; Liu, Jessica C.; Amunugama, Ravindra Nature, Vol. 518, Issue 7538 https://doi.org/10.1038/nature14184	journal	February 2015
The Mouse Genomic Instability Mutation chaos1 Is an Allele of Polq That Exhibits Genetic Interaction with Atm Shima, Naoko; Munroe, Robert J.; Schimenti, John C. Molecular and Cellular Biology, Vol. 24, Issue 23 https://doi.org/10.1128/MCB.24.23.10381-10389.2004	journal	December 2004
POLQ (Pol ), a DNA polymerase and DNA-dependent ATPase in human cells Seki, M. Nucleic Acids Research, Vol. 31, Issue 21 https://doi.org/10.1093/nar/gkg814	journal	November 2003
Reconstructing the coding and non-coding RNA regulatory networks of miRNAs and mRNAs in breast cancer Yang, Sheng; Zhang, Hui; Guo, Li Gene, Vol. 548, Issue 1 https://doi.org/10.1016/j.gene.2014.06.010	journal	September 2014
Structure Casts Light on mtDNA Replication Falkenberg, Maria; Larsson, Nils-Göran Cell, Vol. 139, Issue 2 https://doi.org/10.1016/j.cell.2009.09.030	journal	October 2009
Structure of DNA Polymerase I Klenow Fragment Bound to Duplex DNA Beese, Lorena S.; Derbyshire, Victoria; Steitz, Thomas A. Structural Insights into Gene Expression and Protein Synthesis https://doi.org/10.1142/9789811215865_0028	book	August 2020
TRF2 Interaction with Ku Heterotetramerization Interface Gives Insight into c-NHEJ Prevention at Human Telomeres Ribes-Zamora, Albert; Indiviglio, Sandra M.; Mihalek, Ivana Cell Reports, Vol. 5, Issue 1 https://doi.org/10.1016/j.celrep.2013.08.040	journal	October 2013
A role for DNA polymerase θ in the timing of DNA replication Fernandez-Vidal, Anne; Guitton-Sert, Laure; Cadoret, Jean-Charles Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms5285	journal	July 2014
Arabidopsis TEBICHI, with Helicase and DNA Polymerase Domains, Is Required for Regulated Cell Division and Differentiation in Meristems Inagaki, Soichi; Suzuki, Takamasa; Ohto, Masa-aki The Plant Cell, Vol. 18, Issue 4 https://doi.org/10.1105/tpc.105.036798	journal	March 2006
Single-nucleotide base excision repair DNA polymerase activity in C. elegans in the absence of DNA polymerase Asagoshi, K.; Lehmann, W.; Braithwaite, E. K. Nucleic Acids Research, Vol. 40, Issue 2 https://doi.org/10.1093/nar/gkr727	journal	September 2011
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13641-0	journal	December 2019
Structural Insight into Processive Human Mitochondrial DNA Synthesis and Disease-Related Polymerase Mutations Lee, Young-Sam; Kennedy, W. Dexter; Yin, Y. Whitney Cell, Vol. 139, Issue 4 https://doi.org/10.1016/j.cell.2009.10.026	journal	November 2009
Overexpression of POLQ Confers a Poor Prognosis in Early Breast Cancer Patients Higgins, Geoff S.; Harris, Adrian L.; Prevo, Remko Oncotarget, Vol. 1, Issue 3 https://doi.org/10.18632/oncotarget.124	journal	July 2010
Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination Mateos-Gomez, Pedro A.; Gong, Fade; Nair, Nidhi Nature, Vol. 518, Issue 7538 https://doi.org/10.1038/nature14157	journal	February 2015
Structural Insight into Processive Human Mitochondrial DNA Synthesis and Disease-Related Polymerase Mutations Lee, Young-Sam; Kennedy, W. Dexter; Yin, Y. Whitney Cell, Vol. 139, Issue 2 https://doi.org/10.1016/j.cell.2009.07.050	journal	October 2009
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Phenotype-Based Identification of Mouse Chromosome Instability Mutants Shima, Naoko; Hartford, Suzanne A.; Duffy, Ted Genetics, Vol. 163, Issue 3 https://doi.org/10.1093/genetics/163.3.1031	journal	March 2003
A Small Interfering RNA Screen of Genes Involved in DNA Repair Identifies Tumor-Specific Radiosensitization by POLQ Knockdown Higgins, Geoff S.; Prevo, Remko; Lee, Yin-Fai Cancer Research, Vol. 70, Issue 7 https://doi.org/10.1158/0008-5472.CAN-09-4040	journal	March 2010
DNA replication stress response involving PLK1, CDC6, POLQ, RAD51 and CLASPIN upregulation prognoses the outcome of early/mid-stage non-small cell lung cancer patients Allera-Moreau, C.; Rouquette, I.; Lepage, B. Oncogenesis, Vol. 1, Issue 10 https://doi.org/10.1038/oncsis.2012.29	journal	October 2012
SOLVE and RESOLVE: automated structure solution, density modification and model building Terwilliger, Thomas Journal of Synchrotron Radiation, Vol. 11, Issue 1 https://doi.org/10.1107/S0909049503023938	journal	November 2003
Dual Roles for DNA Polymerase Theta in Alternative End-Joining Repair of Double-Strand Breaks in Drosophila Chan, Sze Ham; Yu, Amy Marie; McVey, Mitch PLoS Genetics, Vol. 6, Issue 7 https://doi.org/10.1371/journal.pgen.1001005	journal	July 2010

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