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Applied Microbiology and Biotechnology

, Volume 102, Issue 15, pp 6409–6424 | Cite as

Affinity maturation of an antibody for the UV-induced DNA lesions 6,4 pyrimidine-pyrimidones

  • Bingjie Kong
  • Yang Cao
  • Danni Wu
  • Lili An
  • Fanlei Ran
  • Yan Lin
  • Chen Ye
  • Hailin Wang
  • Haiying Hang
Biotechnological products and process engineering

Abstract

DNA lesions, associated mostly with minor changes in DNA structure, may induce permanent change in heritable coding information. Biochemically, these minor structural changes are difficult to be explored for generating high-affinity antibodies to detect specific DNA lesions in varying sequence contexts. Herein, we established a platform of bacterial display to facilitate antibodies to be matured with high affinity and high specificity against DNA lesions. To achieve this goal, we, for the first time, developed a two-round mutation/screening strategy: (1) using multiple lesion-containing DNA probes for primary maturation and (2) using single lesion-containing DNA probes for second maturation. Specifically, we capitalized on 64M-2 as a parental template to improve affinity for 6-4PP by 710-fold, compared with the model one. In addition, the matured antibody (9c3) is found to be much less dependent on the bases surrounding 6-4PPs than the model one. The mechanistic study from both computational simulation and reverse mutations revealed the critical roles of the two-round mutations in the enhanced binding affinity and independence of surrounding bases. This selection strategy opens a new way to improve affinity and specificity of antibodies for other DNA lesions.

Keywords

Antibody for DNA lesions Affinity maturation 6,4 Pyrimidine-pyrimidones (6-4PPs) DNA sequence-independent antibody 

Notes

Acknowledgements

We would like to thank Howard B. Lieberman from Columbia University at New York for revising this manuscript, Professor Caixia Guo (Institute of Genomics, Chinese Academy of Sciences) for providing human fibroblasts, Junying Jia and Shuang Sun (Institute of Biophysics, Chinese Academy of Sciences) for their technical assistance in flow cytometry analysis and sorting, and Yuanyuan Chen and Zhenwei Yang (Institute of Biophysics, Chinese Academy of Sciences) for their technical support with Biacore experiments.

Funding information

This work was funded by grants from the Development of Ministry of Science and Technology (No. 2011YQ03013404, No. 2014CB910402) and from the National Natural Science Foundation of China (No. 31500753, No. 31370792, No. 31401130).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

253_2018_8998_MOESM1_ESM.pdf (1.1 mb)
ESM 1 (PDF 1086 kb)

References

  1. Badouard C, Menezo Y, Panteix G, Ravanat JL, Douki T, Cadet J, Favier A (2008) Determination of new types of DNA lesions in human sperm. Zygote 16(1):9–13.  https://doi.org/10.1017/S0967199407004340 CrossRefPubMedGoogle Scholar
  2. Buskila D, Shoenfeld Y (1994) Anti-DNA antibodies. Their idiotypes and SLE. Clin Rev Allergy 12(3):237–252.  https://doi.org/10.1007/BF02802320 PubMedGoogle Scholar
  3. Cadet J, Douki T, Ravanat J-L (2011) Measurement of oxidatively generated base damage in cellular DNA. Mutat Res 711(1–2):3–12.  https://doi.org/10.1016/j.mrfmmm.2011.02.004 CrossRefPubMedGoogle Scholar
  4. Cadet J, Douki T, Ravanat J-L, Wagner JR (2012) Measurement of oxidatively generated base damage to nucleic acids in cells: facts and artifacts. Bioanal Rev 4(2–4):55–74.  https://doi.org/10.1007/s12566-012-0029-6 CrossRefGoogle Scholar
  5. Cao Y, Song L, Miao Z, Hu Y, Tian L, Jiang T (2011) Improved side-chain modeling by coupling clash-detection guided iterative search with rotamer relaxation. Bioinformatics 27(6):785–790.  https://doi.org/10.1093/bioinformatics/btr009 CrossRefPubMedGoogle Scholar
  6. Douki T, Cadet J (2001) Individual determination of the yield of the main UV-induced dimeric pyrimidine photoproducts in DNA suggests a high mutagenicity of CC photolesions. Biochemistry 40(8):2495–2501.  https://doi.org/10.1021/bi0022543 CrossRefPubMedGoogle Scholar
  7. Drablos F, Feyzi E, Aas PA, Vaagbo CB, Kavli B, Bratlie MS, Pena-Diaz J, Otterlei M, Slupphaug G, Krokan HE (2004) Alkylation damage in DNA and RNA—repair mechanisms and medical significance. DNA repair 3(11):1389–1407.  https://doi.org/10.1016/j.dnarep.2004.05.004 CrossRefPubMedGoogle Scholar
  8. EC Friedberg, G Walker, W Siede, RD Wood (2006) DNA repair and mutagenesisGoogle Scholar
  9. Harvey BR, Georgiou G, Hayhurst A, Jeong KJ, Iverson BL, Rogers GK (2004) Anchored periplasmic expression, a versatile technology for the isolation of high-affinity antibodies from Escherichia coli-expressed libraries. Proc Natl Acad Sci U S A 101(25):9193–9198.  https://doi.org/10.1073/pnas.0400187101 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Kobayashi H, Morioka H, Torizawa T, Kato K, Shimada I, Nikaido O, Ohtsuka E (1998) Specificities and rates of binding of anti-(6-4) photoproduct antibody fragments to synthetic thymine photoproducts. J Biochem 123(1):182–188CrossRefPubMedGoogle Scholar
  11. Kuschal C, DiGiovanna JJ, Khan SG, Gatti RA, Kraemer KH (2013) Repair of UV photolesions in xeroderma pigmentosum group C cells induced by translational readthrough of premature termination codons. Proc Natl Acad Sci U S A 110(48):19483–19488.  https://doi.org/10.1073/pnas.1312088110 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Lawley PD, Phillips DH (1996) DNA adducts from chemotherapeutic agents. Mutat Res 355(1–2):13–40.  https://doi.org/10.1016/0027-5107(96)00020-6 CrossRefPubMedGoogle Scholar
  13. Li T, Wang Z, Zhao Y, He W, An L, Liu S, Liu Y, Wang H, Hang H (2013) Checkpoint protein Rad9 plays an important role in nucleotide excision repair. DNA repair 12(4):284–292.  https://doi.org/10.1016/j.dnarep.2013.01.006 CrossRefPubMedGoogle Scholar
  14. Moretti R, Fleishman SJ, Agius R, Torchala M, Bates PA, Kastritis PL, Rodrigues JP, Trellet M, Bonvin AM, Cui M, Rooman M, Gillis D, Dehouck Y, Moal I, Romero-Durana M, Perez-Cano L, Pallara C, Jimenez B, Fernandez-Recio J, Flores S, Pacella M, Praneeth Kilambi K, Gray JJ, Popov P, Grudinin S, Esquivel-Rodriguez J, Kihara D, Zhao N, Korkin D, Zhu X, Demerdash ON, Mitchell JC, Kanamori E, Tsuchiya Y, Nakamura H, Lee H, Park H, Seok C, Sarmiento J, Liang S, Teraguchi S, Standley DM, Shimoyama H, Terashi G, Takeda-Shitaka M, Iwadate M, Umeyama H, Beglov D, Hall DR, Kozakov D, Vajda S, Pierce BG, Hwang H, Vreven T, Weng Z, Huang Y, Li H, Yang X, Ji X, Liu S, Xiao Y, Zacharias M, Qin S, Zhou HX, Huang SY, Zou X, Velankar S, Janin J, Wodak SJ, Baker D (2013) Community-wide evaluation of methods for predicting the effect of mutations on protein–protein interactions. Proteins 81(11):1980–1987.  https://doi.org/10.1002/prot.24356 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Mori T, Nakane M, Hattori T, Matsunaga T, Ihara M, Nikaido O (1991) Simultaneous establishment of monoclonal-antibodies specific for either cyclobutane pyrimidine dimer or (6-4)photoproduct from the same mouse immunized with ultraviolet-irradiated DNA. Photochem Photobiol 54(2):225–232.  https://doi.org/10.1111/j.1751-1097.1991.tb02010.x CrossRefPubMedGoogle Scholar
  16. Nie B, Gan W, Shi F, Hu GX, Chen LG, Hayakawa H, Sekiguchi M, Cai JP (2013) Age-dependent accumulation of 8-oxoguanine in the DNA and RNA in various rat tissues. Oxidative Med Cell Longev 2013:303181.  https://doi.org/10.1155/2013/303181 CrossRefGoogle Scholar
  17. Renaud E, Miccoli L, Zacal N, Biard DS, Craescu CT, Rainbow AJ, Angulo JF (2011) Differential contribution of XPC, RAD23A, RAD23B and CENTRIN 2 to the UV-response in human cells. DNA repair 10(8):835–847.  https://doi.org/10.1016/j.dnarep.2011.05.003 CrossRefPubMedGoogle Scholar
  18. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273(10):5858–5868.  https://doi.org/10.1074/jbc.273.10.5858 CrossRefPubMedGoogle Scholar
  19. Rossner P Jr, Orhan H, Koppen G, Sakai K, Santella RM, Ambroz A, Rossnerova A, Sram RJ, Ciganek M, Neca J, Arzuk E, Mutlu N, Cooke MS (2016) Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine analysis by an improved ELISA: an inter-laboratory comparison study. Free Radic Biol Med 95:169–179.  https://doi.org/10.1016/j.freeradbiomed.2016.03.016 CrossRefPubMedGoogle Scholar
  20. Sikorav JL, Auffray C, Rougeon F (1980) Structure of the constant and 3′ untranslated regions of the murine Balb/c gamma 2a heavy chain messenger RNA. Nucleic Acids Res 8(14):3143–3155.  https://doi.org/10.1093/nar/8.14.3143 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Sun S, Yang X, Wang H, Zhao Y, Lin Y, Ye C, Fang X, Hang H (2016) Antibody affinity maturation through combining display of two-chain paired antibody and precision flow cytometric sorting. Appl Microbiol Biotechnol 100(13):5977–5988.  https://doi.org/10.1007/s00253-016-7472-1 CrossRefPubMedGoogle Scholar
  22. Svasti J, Milstein C (1972) The complete amino acid sequence of a mouse kappa light chain. Biochem J 128(2):427–444.  https://doi.org/10.1042/bj1280427 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Swindells MB, Porter CT, Couch M, Hurst J, Abhinandan KR, Nielsen JH, Macindoe G, Hetherington J, Martin AC (2017) abYsis: integrated antibody sequence and structure-management, analysis, and prediction. J Mol Biol 429(3):356–364.  https://doi.org/10.1016/j.jmb.2016.08.019 CrossRefPubMedGoogle Scholar
  24. ter Borg EJ, Horst G, Hummel EJ, Limburg PC, Kallenberg CG (1990) Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus. A long-term, prospective study. Arthritis Rheum 33(5):634–643.  https://doi.org/10.1002/art.1780330505 CrossRefPubMedGoogle Scholar
  25. Ting D, Wang G, Shapovalov M, Mitra R, Jordan MI, Dunbrack RL Jr (2010) Neighbor-dependent Ramachandran probability distributions of amino acids developed from a hierarchical Dirichlet process model. PLoS Comput Biol 6(4):e1000763.  https://doi.org/10.1371/journal.pcbi.1000763 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Wang QE, Zhu QZ, Wani MA, Wani G, Chen JM, Wani AA (2003) Tumor suppressor p53 dependent recruitment of nucleotide excision repair factors XPC and TFIIH to DNA damage. DNA Repair 2(5):483–499.  https://doi.org/10.1016/S1568-7864(03)00002-8 CrossRefPubMedGoogle Scholar
  27. Yao XQ, Scarabelli G, Skjrven L, Grant BJ (2014) The Bio3D package: new interactive tools for structural bioinformatics. Biophys J 106(2):406a–406a.  https://doi.org/10.1016/j.bpj.2013.11.2288 CrossRefGoogle Scholar
  28. Yokoyama H, Mizutani R, Satow Y, Sato K, Komatsu Y, Ohtsuka E, Nikaido O (2012) Structure of the DNA (6-4) photoproduct dTT(6-4)TT in complex with the 64M-2 antibody Fab fragment implies increased antibody-binding affinity by the flanking nucleotides. Acta Crystallogr D Biol Crystallogr 68:232–238.  https://doi.org/10.1107/S0907444912000327 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Bingjie Kong
    • 1
    • 2
  • Yang Cao
    • 3
  • Danni Wu
    • 2
    • 4
  • Lili An
    • 1
  • Fanlei Ran
    • 1
  • Yan Lin
    • 5
  • Chen Ye
    • 1
  • Hailin Wang
    • 2
    • 4
  • Haiying Hang
    • 1
    • 2
  1. 1.Key Laboratory for Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of BiophysicsChinese Academy of SciencesBeijingChina
  2. 2.University of Chinese Academy of SciencesBeijingChina
  3. 3.Center of Growth, Metabolism and Aging, Key Lab of Bio-Resources and Eco-Environment of Ministry of Education, College of Life SciencesSichuan UniversityChengduChina
  4. 4.State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijingChina
  5. 5.College of Bee ScienceFujian Agriculture and Forestry UniversityFuzhouChina

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