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Cited by 3DNA Repair MechanismsEnzyme Structure and FunctionPARP inhibition in cancer therapy

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Zebrafish Polymerase Theta and human Polymerase Theta: Orthologues with homologous function

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Thomas, Corey, Green, Sydney, Kimball, Lily, Schmidtke, Isaiah R., Rothwell, Lauren, Griffin, Makayla, Par, Ivy, Schobel, Sophia, Palacio, Yayleene, Towle-Weicksel, Jamie B., Weicksel, Steven E.·2025·PLOS One
DOI 10.1371/journal.pone.0321886PMC PMC12040184

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Abstract

DNA Polymerase Theta (Pol θ) is a conserved an A-family polymerase that plays an essential role in repairing double strand breaks, through micro-homology end joining, and bypassing DNA lesions, through translesion synthesis, to protect genome integrity. Despite its essential role in DNA repair, Pol θ is inherently error-prone. Recently, key loop regions were identified to play an important role in key functions of Pol θ. Here we present a comparative structure-function study of the polymerase domain of zebrafish and human Pol θ. We show that these two proteins share a large amount of sequence and structural homology. Using a classical biochemical approach we observe that zebrafish Pol θ displays behavior characteristic of human Pol θ, including DNA template extension in the presence of different divalent metals, microhomology-mediated end joining, and translesion synthesis. These results will support future studies looking to gain insight into Pol θ function on the basis of evolutionarily conserved features.

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Figures

Fig 1 Structural modeling of zPol θ PD. (A) AlphaFold rendering of zPol θ PD with subdomains colored, thumb residues 2093-2217 – blue, fingers residues 2327-2468 – red, palm – residues 2217-2252; 2469-2576 green, and exo-nuclease residues 1832-2093 – yellow. DNA is colored in light blue. (B) FATCAT overlay of AlphaFold rending of zPol θ PD (bronze) and hPol θ PD (navy) crystal structure [21] without loop inserts. DNA is colored in light blue. PDB 4X0Q.
Fig 1 Structural modeling of zPol θ PD. (A) AlphaFold rendering of zPol θ PD with subdomains colored, thumb residues 2093-2217 – blue, fingers residues 2327-2468 – red, palm – residues 2217-2252; 2469-2576 green, and exo-nuclease residues 1832-2093 – yellow. DNA is colored in light blue. (B) FATCAT overlay of AlphaFold rending of zPol θ PD (bronze) and hPol θ PD (navy) crystal structure [21] without loop inserts. DNA is colored in light blue. PDB 4X0Q.CC BY · PubMed Central
Fig 2 hPol θ and zPol θ PDs display similar secondary characteristics and thermal stability. (A) SDS-PAGE of purified hPol θ PD and zPol θ PD. Expression and purification of zPol θ PD was the same as hPol θ PD as described in the Materials and Methods. For each sample, approximately 56–60 pmol of cleaved, purified protein were loaded on a 10% SDS PAGE and Coomassie stained. Both hPol θ and zPol θ PD fragments migrate to approximately 90 kDa as expected. (B) Circular dichroism spectra of 3 μM hPol θ PD (solid line) and zPol θ PD (dashed) proteins in 10 mM Potassium Phosphate buffer. Samples were scanned from 190 to 280 nm. (C) The same samples were heated from 20–90°C and ellipticity measured at 222 nm.
Fig 2 hPol θ and zPol θ PDs display similar secondary characteristics and thermal stability. (A) SDS-PAGE of purified hPol θ PD and zPol θ PD. Expression and purification of zPol θ PD was the same as hPol θ PD as described in the Materials and Methods. For each sample, approximately 56–60 pmol of cleaved, purified protein were loaded on a 10% SDS PAGE and Coomassie stained. Both hPol θ and zPol θ PD fragments migrate to approximately 90 kDa as expected. (B) Circular dichroism spectra of 3 μM hPol θ PD (solid line) and zPol θ PD (dashed) proteins in 10 mM Potassium Phosphate buffer. Samples were scanned from 190 to 280 nm. (C) The same samples were heated from 20–90°C and ellipticity measured at 222 nm.CC BY · PubMed Central
Fig 3 zPol θ PD binds tightly to dsDNA. zPol θ PD was titrated from 0–1000 nM against 10 nM 25/40 dsDNA. Bound and unbound products were separated on a 6% non-denaturing gel and quantified using ImageQuant. KD(DNA) was mathematically calculated using Equation 1 and is the midpoint between bound and unbound fractions.
Fig 3 zPol θ PD binds tightly to dsDNA. zPol θ PD was titrated from 0–1000 nM against 10 nM 25/40 dsDNA. Bound and unbound products were separated on a 6% non-denaturing gel and quantified using ImageQuant. KD(DNA) was mathematically calculated using Equation 1 and is the midpoint between bound and unbound fractions.CC BY · PubMed Central
Fig 4 zPol θ PD experiences greater nucleotide extension activity compared to hPol θ PD. Denaturing gel showing primer extension dsDNA substrate with MgCl2 and MnCl2. (A) Under steady-state conditions 50 nM hPol θ or zPol θ PD proteins were preincubated with 200 nM 25/40 dsDNA and combined with either 10 mM MgCl2 or MnCl2 for 5 minutes at 37°C. (B) The assay was repeated under steady-state conditions, with 10 nM Pol θ and 25 nM 25/40 dsDNA. Reactions were initiated with 100 µM dNTPs, 10 mM MgCl2 or MnCl2, and 75-fold excess of unlabeled 25/40 dsDNA for 5 minutes at 37°C (indicated by a *). DNA extension products were separated on a denaturing gel and visualized on a Typhoon scanner. Each n+1 band represents an extension of one nucleotide following the DNA template as described above. n+1 would represent either correct nucleotide incorporation of dCTP opposite a templating G (underlined) or a misincorporation event of dATP, dGTP, or dTTP opposite templating G. Each subsequent band is another nucleotide extension with a maximum template-dependent extension of n+18. Bands migrating higher than n+18 represent de novo synthesis.
Fig 4 zPol θ PD experiences greater nucleotide extension activity compared to hPol θ PD. Denaturing gel showing primer extension dsDNA substrate with MgCl2 and MnCl2. (A) Under steady-state conditions 50 nM hPol θ or zPol θ PD proteins were preincubated with 200 nM 25/40 dsDNA and combined with either 10 mM MgCl2 or MnCl2 for 5 minutes at 37°C. (B) The assay was repeated under steady-state conditions, with 10 nM Pol θ and 25 nM 25/40 dsDNA. Reactions were initiated with 100 µM dNTPs, 10 mM MgCl2 or MnCl2, and 75-fold excess of unlabeled 25/40 dsDNA for 5 minutes at 37°C (indicated by a *). DNA extension products were separated on a denaturing gel and visualized on a Typhoon scanner. Each n+1 band represents an extension of one nucleotide following the DNA template as described above. n+1 would represent either correct nucleotide incorporation of dCTP opposite a templating G (underlined) or a misincorporation event of dATP, dGTP, or dTTP opposite templating G. Each subsequent band is another nucleotide extension with a maximum template-dependent extension of n+18. Bands migrating higher than n+18 represent de novo synthesis.CC BY · PubMed Central
Fig 5 zPol θ PD experiences biphasic burst activity. ZPol θ PD (100 nM) was preincubated with 300 nM 25/40 dsDNA. The DNA/Pol θ PD complex was rapidly combined with 100 μM dCTP (correct nucleotide) and 10 mM MgCl2. Reactions were carried out at 37°C and quenched with 0.5 M EDTA. Products were separated on a denaturing gel and quantified with ImageQuant software. Data were fit to a biphasic burst equation to obtain observed kobs rates 15.9 ± s-1. The slower rate kss was calculated to be 3.4 ± 0.46 s-1.
Fig 5 zPol θ PD experiences biphasic burst activity. ZPol θ PD (100 nM) was preincubated with 300 nM 25/40 dsDNA. The DNA/Pol θ PD complex was rapidly combined with 100 μM dCTP (correct nucleotide) and 10 mM MgCl2. Reactions were carried out at 37°C and quenched with 0.5 M EDTA. Products were separated on a denaturing gel and quantified with ImageQuant software. Data were fit to a biphasic burst equation to obtain observed kobs rates 15.9 ± s-1. The slower rate kss was calculated to be 3.4 ± 0.46 s-1.CC BY · PubMed Central
Fig 6 zPol θ PD is able to perform MMEJ activity of short DNA fragments. Non-Denaturing gel demonstrating alignment and extension of ssDNA. zPol θ PD (20 nM) was preincubated with 30 nM 5’-FAM 12-mer ssDNA in reaction buffer. Samples either had all nucleotides (+dNTP) or no nucleotides (-dNTP) added and the ternary complex was incubated for 45 minutes at 37°C. Reactions were stopped and products separated on a 12% Native PAGE. The gel was visualized on a Typhoon scanner. MMEJ products are indicated, as well as smaller snap-back products indicated by the bracket.
Fig 6 zPol θ PD is able to perform MMEJ activity of short DNA fragments. Non-Denaturing gel demonstrating alignment and extension of ssDNA. zPol θ PD (20 nM) was preincubated with 30 nM 5’-FAM 12-mer ssDNA in reaction buffer. Samples either had all nucleotides (+dNTP) or no nucleotides (-dNTP) added and the ternary complex was incubated for 45 minutes at 37°C. Reactions were stopped and products separated on a 12% Native PAGE. The gel was visualized on a Typhoon scanner. MMEJ products are indicated, as well as smaller snap-back products indicated by the bracket.CC BY · PubMed Central
Fig 7 zPol θ PD is able to bypass DNA lesions. Denaturing gel demonstrating primer extension on damaged dsDNA substrates with MgCl2 and MnCl2.As described in the Materials and Methods, 200 nM hPol θ and zPol θ PDs were preincubated with 50 nM DNA substrate, (A) Undamaged (TT), (B) CPD (TT), (C) Abasic ((AP)T), (D) 8-oxo-dG ((8-oxo-dGT)T). Reactions were initiated by the addition of 125 nM dNTPs as described and either 10 mM MgCl2 or MnCl2. Reactions were carried out at 37°C for 5 minutes and products visualized on a 12% denaturing gel. Higher migrating products are indicative of full extension (n+12) with smeared bands representing de novo synthesis with extension past n+12.
Fig 7 zPol θ PD is able to bypass DNA lesions. Denaturing gel demonstrating primer extension on damaged dsDNA substrates with MgCl2 and MnCl2.As described in the Materials and Methods, 200 nM hPol θ and zPol θ PDs were preincubated with 50 nM DNA substrate, (A) Undamaged (TT), (B) CPD (TT), (C) Abasic ((AP)T), (D) 8-oxo-dG ((8-oxo-dGT)T). Reactions were initiated by the addition of 125 nM dNTPs as described and either 10 mM MgCl2 or MnCl2. Reactions were carried out at 37°C for 5 minutes and products visualized on a 12% denaturing gel. Higher migrating products are indicative of full extension (n+12) with smeared bands representing de novo synthesis with extension past n+12.CC BY · PubMed Central
Fig 8 DNA Pol θ PD is able incorporate and extend dsDNA in the presence of Ca2+. Denaturing gel showing primer extension dsDNA substrate with CaCl2. Under single turnover conditions 200 nM Pol θ PD (human or zebrafish) was preincubated with 50 nM 24/33 undamaged (A) or damaged (B) DNA substrate and reacted with 125 nM nucleotides in 10 mM CaCl2. Reactions were carried out at 37°C for 5 minutes and products visualized on a 12% denaturing gel. Percent extended was calculated using ImageQuant software by quantifying the intensity of the extended products (n+1 and higher) divided by the intensity of the total amount of DNA.
Fig 8 DNA Pol θ PD is able incorporate and extend dsDNA in the presence of Ca2+. Denaturing gel showing primer extension dsDNA substrate with CaCl2. Under single turnover conditions 200 nM Pol θ PD (human or zebrafish) was preincubated with 50 nM 24/33 undamaged (A) or damaged (B) DNA substrate and reacted with 125 nM nucleotides in 10 mM CaCl2. Reactions were carried out at 37°C for 5 minutes and products visualized on a 12% denaturing gel. Percent extended was calculated using ImageQuant software by quantifying the intensity of the extended products (n+1 and higher) divided by the intensity of the total amount of DNA.CC BY · PubMed Central

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Research works printed but not linked: 50

  1. LA Loeb, 2003, Multiple mutations and cancer, Proc Natl Acad Sci U S A, 100, 776, 10.1073/pnas.0334858100 · DOI
  2. C Vaziri, 2021, Unravelling roles of error-prone DNA polymerases in shaping cancer genomes, Oncogene, 40, 6549, 10.1038/s41388-021-02032-9 · DOI
  3. SS Lange, 2011, DNA polymerases and cancer, Nat Rev Cancer, 11, 96, 10.1038/nrc2998 · DOI · Paper page
  4. TA Kunkel, 2003, Considering the cancer consequences of altered DNA polymerase function, Cancer Cell, 3, 105, 10.1016/S1535-6108(03)00027-8 · DOI
  5. F Farshidfar, 2022, Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis, Nature Communications, 13, 898, 10.1038/s41467-022-28566-4 · DOI
  6. SB Thyme, 2016, Polq-mediated end joining is essential for surviving DNA double-strand breaks during early zebrafish development, Cell Rep, 15, 707, 10.1016/j.celrep.2016.03.072 · DOI
  7. A Brambati, 2020, DNA polymerase theta (Polθ) - an error-prone polymerase necessary for genome stability, Curr Opin Genet Dev, 60, 119, 10.1016/j.gde.2020.02.017 · DOI
  8. J-H Yoon, 2019, Error-prone replication through UV lesions by DNA polymerase θ protects against skin cancers, Cell, 176, 1295-1309.e15
  9. SH Chan, 2010, Dual roles for DNA polymerase theta in alternative end-joining repair of double-strand breaks in Drosophila, PLoS Genet, 6, e1001005, 10.1371/journal.pgen.1001005 · DOI
  10. T Kent, 2015, Mechanism of microhomology-mediated end-joining promoted by human DNA polymerase θ, Nat Struct Mol Biol, 22, 230, 10.1038/nsmb.2961 · DOI
  11. MJ Yousefzadeh, 2014, Mechanism of suppression of chromosomal instability by DNA polymerase POLQ, PLoS Genet, 10, e1004654, 10.1371/journal.pgen.1004654 · DOI
  12. M Hogg, 2011, Lesion bypass activity of DNA polymerase θ (POLQ) is an intrinsic property of the pol domain and depends on unique sequence inserts, J Mol Biol, 405, 642, 10.1016/j.jmb.2010.10.041 · DOI
  13. AM Yu, 2010, Synthesis-dependent microhomology-mediated end joining accounts for multiple types of repair junctions, Nucleic Acids Res, 38, 5706, 10.1093/nar/gkq379 · DOI
  14. R Ceccaldi, 2015, Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair, Nature, 518, 258, 10.1038/nature14184 · DOI
  15. J Goff, 2009, Lack of DNA Polymerase θ (POLQ) radiosensitizes bone marrow stromal cells in vitro and increases reticulocyte micronuclei after total-body irradiation, Radiation Research, 172, 165, 10.1667/RR1598.1 · DOI
  16. T Goullet de Rugy, 2016, Excess Polθ functions in response to replicative stress in homologous recombination-proficient cancer cells, Biol Open, 5, 1485, 10.1242/bio.018028 · DOI
  17. C Allera-Moreau, 2012, 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, Oncogenesis, 1, e30, 10.1038/oncsis.2012.29 · DOI
  18. F Lemée, 2010, DNA polymerase theta up-regulation is associated with poor survival in breast cancer, perturbs DNA replication, and promotes genetic instability, Proc Natl Acad Sci U S A, 107, 13390, 10.1073/pnas.0910759107 · DOI
  19. K Howe, 2013, The zebrafish reference genome sequence and its relationship to the human genome, Nature, 496, 498, 10.1038/nature12111 · DOI · Paper page
  20. M Mirdita, 2022, ColabFold: making protein folding accessible to all, Nat Methods, 19, 679, 10.1038/s41592-022-01488-1 · DOI · Paper page
  21. KE Zahn, 2015, Human DNA polymerase θ grasps the primer terminus to mediate DNA repair, Nat Struct Mol Biol, 22, 304, 10.1038/nsmb.2993 · DOI
  22. K Johnson, 1992, Transient-state kinetic analysis of enzyme reaction pathways, Enzymes, 20, 1
  23. T Kent, 2016, Polymerase θ is a robust terminal transferase that oscillates between three different mechanisms during end-joining, eLife, 5, e13740, 10.7554/eLife.13740 · DOI
  24. CM Joyce, 2010, Techniques used to study the DNA polymerase reaction pathway, Biochim Biophys Acta, 1032, 10.1016/j.bbapap.2009.07.021 · DOI
  25. SJ Black, 2019, Molecular basis of microhomology-mediated end-joining by purified full-length Polθ, Nat Commun, 10, 4423, 10.1038/s41467-019-12272-9 · DOI
  26. C Li, 2023, Structural basis of DNA polymerase θ mediated DNA end joining, Nucleic Acids Res, 51, 463, 10.1093/nar/gkac1201 · DOI
  27. G Chandramouly, 2023, Polλ promotes microhomology-mediated end-joining, Nat Struct Mol Biol, 30, 107, 10.1038/s41594-022-00895-4 · DOI
  28. D Carvajal-Maldonado, 2024, Dynamic stem-loop extension by Pol θ and templated insertion during DNA repair, J Biol Chem, 300, 107461, 10.1016/j.jbc.2024.107461 · DOI
  29. M Seki, 2004, High-efficiency bypass of DNA damage by human DNA polymerase Q, EMBO J, 23, 4484, 10.1038/sj.emboj.7600424 · DOI
  30. DJ Laverty, 2017, The A-rule and deletion formation during abasic and oxidized abasic site bypass by DNA polymerase θ, ACS Chem Biol, 12, 1584, 10.1021/acschembio.7b00211 · DOI
  31. J-H Yoon, 2020, Genetic evidence for reconfiguration of DNA polymerase θ active site for error-free translesion synthesis in human cells, J Biol Chem, 295, 5918, 10.1074/jbc.RA120.012816 · DOI
  32. BD Freudenthal, 2013, Observing a DNA polymerase choose right from wrong, Cell, 154, 157, 10.1016/j.cell.2013.05.048 · DOI
  33. T Nakamura, 2012, Watching DNA polymerase η make a phosphodiester bond, Nature, 487, 196, 10.1038/nature11181 · DOI
  34. D-S Pei, 2011, A novel regulatory circuit in base excision repair involving AP endonuclease 1, Creb1 and DNA polymerase beta, Nucleic Acids Res, 39, 3156, 10.1093/nar/gkq1142 · DOI
  35. S Fortier, 2009, Base excision repair in early zebrafish development: evidence for DNA polymerase switching and standby AP endonuclease activity, Biochemistry, 48, 5396, 10.1021/bi900253d · DOI
  36. R Brañas Casas, 2024, Zebrafish polg2 knock-out recapitulates human POLG-disorders; implications for drug treatment, Cell Death Dis, 15, 281, 10.1038/s41419-024-06622-9 · DOI
  37. N Plaster, 2006, p53 deficiency rescues apoptosis and differentiation of multiple cell types in zebrafish flathead mutants deficient for zygotic DNA polymerase delta1, Cell Death Differ, 13, 223, 10.1038/sj.cdd.4401747 · DOI
  38. T Ishido, 2011, Characterization of DNA polymerase β from Danio rerio by overexpression in E. coli using the in vivo/in vitro compatible pIVEX plasmid, Microb Cell Fact, 10, 84, 10.1186/1475-2859-10-84 · DOI
  39. C Thomas, 2024, Melanoma-derived DNA polymerase theta variants exhibit altered DNA polymerase activity, Biochemistry, 63, 1107, 10.1021/acs.biochem.3c00670 · DOI
  40. JB Towle-Weicksel, 2014, Fluorescence resonance energy transfer studies of DNA polymerase β: the critical role of fingers domain movements and a novel non-covalent step during nucleotide selection, J Biol Chem, 289, 16541, 10.1074/jbc.M114.561878 · DOI
  41. BG Werneburg, 1996, DNA polymerase beta: pre-steady-state kinetic analysis and roles of arginine-283 in catalysis and fidelity, Biochemistry, 35, 7041, 10.1021/bi9527202 · DOI
  42. DL Murphy, 2008, The Asp285 variant of DNA polymerase beta extends mispaired primer termini via increased nucleotide binding, Biochemistry, 47, 8048, 10.1021/bi702104y · DOI
  43. C Ralec, 2017, Calcium-driven DNA synthesis by a high-fidelity DNA polymerase, Nucleic Acids Res, 45, 12425, 10.1093/nar/gkx927 · DOI
  44. AJ Guerin, 2024, High-resolution freshwater dissolved calcium and pH data layers for Canada and the United States, Sci Data, 11, 370, 10.1038/s41597-024-03165-8 · DOI
  45. F Madeira, 2024, The EMBL-EBI Job Dispatcher sequence analysis tools framework in 2024, Nucleic Acids Res, 52, W521, 10.1093/nar/gkae241 · DOI
  46. M Mirdita, 2019, MMseqs2 desktop and local web server app for fast, interactive sequence searches, Bioinformatics, 35, 2856, 10.1093/bioinformatics/bty1057 · DOI · Paper page
  47. M Mirdita, 2017, Uniclust databases of clustered and deeply annotated protein sequences and alignments, Nucleic Acids Res, 45, D170, 10.1093/nar/gkw1081 · DOI
  48. AL Mitchell, 2019, MGnify: the microbiome analysis resource in 2020, Nucleic Acids Res
  49. S Bittrich, 2024, RCSB protein Data Bank: exploring protein 3D similarities via comprehensive structural alignments, Bioinformatics, 40, btae370, 10.1093/bioinformatics/btae370 · DOI
  50. R Prasad, 2009, Human DNA polymerase theta possesses 5’-dRP lyase activity and functions in single-nucleotide base excision repair in vitro, Nucleic Acids Res, 37, 1868, 10.1093/nar/gkp035 · DOI

Metadata

Authors
Thomas, C., Green, S., Kimball, L., Schmidtke, I. R., Rothwell, L., Griffin, M., Par, I., Schobel, S., Palacio, Y., Towle-Weicksel, J. B., & Weicksel, S. E.
Affiliations
  • Rhode Island College (US)
  • Bryant University (US)
Corresponding author
Weicksel, Steven E.
ORCID
Venue
PLOS One
Publisher
Public Library of Science (PLoS)
Published
2025-04-29
Volume
20
Issue
4
Pages
e0321886
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0321886
PMC
PMC12040184
OpenAlex
W4409915590
Cited by
3
References
3
Citations by year
2026: 1 · 2025: 1
FWCI
0.60
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Rhode Island IDeA Networks of Biomedical Research Excellence (P20GM103430)
  • National Institute of General Medical Sciences (R15GM144903-01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
  • Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Keywords
DNA polymerase theta, zebrafish, human, microhomology-mediated end joining, translesion synthesis, DNA double-strand break repair, divalent metal ions, structure functions, evolutionary conservation, genome stability

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Thomas, C., Green, S., Kimball, L., Schmidtke, I. R., Rothwell, L., Griffin, M., Par, I., Schobel, S., Palacio, Y., Towle-Weicksel, J. B., & Weicksel, S. E. (2025). Zebrafish Polymerase Theta and human Polymerase Theta: Orthologues with homologous function. PLOS One. https://doi.org/10.1371/journal.pone.0321886