PARP1 Binding to DNA Breaks and Hairpins Alters Nucleosome Structure

  • N. V. MalyuchenkoEmail author
  • E. Yu. Kotova
  • M. P. Kirpichnikov
  • V. M. Studitsky
  • A. V. Feofanov


Poly(ADP-ribose)polymerase 1 (PARP1) is involved in the processes of DNA repair, replication, transcription, cell cycle regulation, and apoptosis. Participation of PARP1 in DNA repair is determined by the ability of the enzyme to interact with various damages and noncanonical structures of DNA with consequent polyADP-ribosylation of neighboring proteins. Earlier, for mononucleosomes containing a DNA end recapitulating double-strand DNA break near the nucleosome, it was found that PARP1 induces nucleosome structural changes in the absence of NAD+. In the present work, it is reported that PARP1 induces similar structural changes in nucleosomes containing either DNA ends extending from the core by 20 bp or containing hairpins at the DNA ends. In all the cases, PARP1 caused changes in DNA wrapping on the surface of the histone octamer that are accompanied by an increase in the distance between adjacent DNA gyres. These PARP1-mediated changes in the nucleosome structure presumably contribute to chromatin decondensation and facilitate access of repair enzymes to damaged DNA.


poly(ADP-ribose)polymerase 1 nucleosome fluorescence energy transfer microscopy DNA hairpins. 



This work was performed with the support from the Russian Foundation for Basic Research, project no. 17-54-33045.


The authors declare that they have no conflict of interest.


The study was performed without the use of animals and without involving people as subjects.


  1. 1.
    Ludwig, A., Behnke, B., Holtlund, J., and Hilz, H., Immunoquantitation and size determination of intrinsic poly(ADP-ribose) polymerase from acid precipitates. An analysis of the in vivo status in mammalian species and in lower eukaryotes, J. Biol. Chem., 1988, vol. 263, no. 15, pp. 6993–6999.PubMedGoogle Scholar
  2. 2.
    Ame, J.C., Spenlehauer, C., and de Murcia, G., The PARP superfamily, BioEssays, 2004, vol. 26, no. 8, pp. 882–893.CrossRefGoogle Scholar
  3. 3.
    Langelier, M.F., Planck, J.L., Roy, S., and Pascal, J.M., Structural basis for DNA damage-dependent poly(ADP-ribosyl)ation by human PARP-1, Science, 2012, vol. 336, no. 6082, pp. 728–732.CrossRefGoogle Scholar
  4. 4.
    Langelier, M.F., Eisemann, T., Riccio, A.A., and Pascal, J.M., PARP family enzymes: Regulation and catalysis of the poly(ADP-ribose) posttranslational modification, Curr. Opin. Struct. Biol., 2018, vol. 53, pp. 187–198.CrossRefGoogle Scholar
  5. 5.
    Pion, E., Ullmann, G.M., Amé, J.C., Gérard, D., de Murcia, G., and Bombarda, E., DNA-induced dimerization of poly(ADP-ribose) polymerase-1 triggers its activation, Biochemistry, 2005, vol. 44, no. 44, pp. 14670–14681.CrossRefGoogle Scholar
  6. 6.
    Pascal, J.M., The comings and goings of PARP-1 in response to DNA damage, DNA Repair (Amsterdam), 2018, vol. 71, pp. 177–182.CrossRefGoogle Scholar
  7. 7.
    Haince, J.F., McDonald, D., Rodrigue, A., Dery, U., Masson, J.Y., Hendzel, M.J., and Poirierg, G.G., PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites, J. Biol. Chem., 2008, vol. 283, no. 2, pp. 1197–1208.CrossRefGoogle Scholar
  8. 8.
    Liu, C., Vyas, A., Kassab, M.A., Singh, A.K., and Yu, X., The role of poly ADP-ribosylation in the first wave of DNA damage response, Nucleic Acid Res., 2017, vol. 45, no. 14, pp. 8129–8141.CrossRefGoogle Scholar
  9. 9.
    Sultanov, D.C., Gerasimova, N.S., Kudryashova, K.S., Maluchenko, N.V., Kotova, E.Y., Langelier, M.F., Pascal, J.M., Kirpichnikov, M.P., Feofanov, A.V., and Studitsky, V.M., Unfolding of core nucleosomes by PARP-1 revealed by spFRET microscopy, AIMS Genet., 2017, vol. 4, no. 1, pp. 21–31.CrossRefGoogle Scholar
  10. 10.
    Liu, Z. and Kraus, K.W., Catalytic-independent functions of PARP-1 determine Sox2 pioneer activity at intractable genomic loci, Mol. Cell, 2017, vol. 65, no. 4, pp. 589–603.CrossRefGoogle Scholar
  11. 11.
    Valieva, M.E., Armeev, G.A., Kudryashova, K.S., Gerasimova, N.S., Shaytan, A.K., Kulaeva, O.I., McCullough, L.L., Formosa, T., Georgiev, P.G., Kirpichnikov, M.P., Studitsky, V.M., and Feofanov, A.V., Large-scale ATP-independent nucleosome unfolding by a histone chaperone, Nat. Struct. Mol. Biol., 2016, vol. 23, no. 12, pp. 1111–1116.CrossRefGoogle Scholar
  12. 12.
    Valieva, M.E., Gerasimova, N.S., Kudryashova, K.S., Kozlova, A.L., Kirpichnikov, M.P., Hu, Q., Botuyan, M.V., Mer, G., Feofanov, A.V., and Studitsky, V.M., Stabilization of nucleosomes by histone tails and by FACT revealed by spFRET microscopy, Cancers, 2017, vol. 9, no. 1, p. 3.CrossRefGoogle Scholar
  13. 13.
    Gaykalova, D.A., Kulaeva, O.I., Bondarenko, V.A., and Studitsky, V.M., Preparation and analysis of uniquely positioned mononucleosomes, Methods Mol. Biol., 2009, vol. 523, pp. 109–123.CrossRefGoogle Scholar
  14. 14.
    Langelier, M.F., Steffen, J., Riccio, A.A., McCauley, M., and Pascal, J.M., Purification of DNA damage-dependent PARPs from E. coli for structural and biochemical analysis, Methods Mol. Biol., vol. 1608, pp. 431–444.Google Scholar
  15. 15.
    Kudryashova, K.S., Nikitin, D.V., Chertkov, O.V., Gerasimova, N.S., Valeva, M.E., Studitsky, V.M., and Feofanov, A.V., Development of fluorescently labeled mononucleosomes for the investigation of transcription mechanisms by single complex microscopy, Moscow Univ. Biol. Sci. Bull., 2015, vol. 70, no. 4, pp. 189–193.CrossRefGoogle Scholar
  16. 16.
    Kudryashova, K.S., Chertkov, O.V., Nikitin, D.V., Pestov, N.A., Kulaeva, O.I., Efremenko, A.V., Solonin, A.S., Kirpichnikov, M.P., Studitsky, V.M., and Feofanov, A.V., Preparation of mononucleosomal templates for analysis of transcription with RNA polymerase using spFRET, Methods Mol. Biol., vol. 1288, pp. 395–412.Google Scholar
  17. 17.
    Polach, K.J. and Widom, J., Mechanism of protein access to specific DNA sequences in chromatin: A dynamic equilibrium model for gene regulation, J. Mol. Biol., 1995, vol. 254, no. 2, pp. 130–149.CrossRefGoogle Scholar
  18. 18.
    Clark, N.J., Kramer, M., Muthurajan, U.M., and Luger, K., Alternative modes of binding of poly(ADP-ribose) polymerase 1 to free DNA and nucleosomes, J. Biol. Chem., 2012, vol. 287, no. 39, pp. 32430–32439.CrossRefGoogle Scholar
  19. 19.
    Potaman, V.N., Shlyakhtenko, L.S., Oussatcheva, E.A., Lyubchenko, Y.L., and Soldatenkov, V.A., Specific binding of poly(ADP-ribose) polymerase-1 to cruciform hairpins, J. Mol. Biol., 2005, vol. 348, no. 3, pp. 609–661.CrossRefGoogle Scholar
  20. 20.
    Muthurajan, U.M., Hepler, M.R., Hieb, A.R., Clark, N.J., Kramer, M., Yao, T., and Luger, K., Automodification switches PARP-1 function from chromatin architectural protein to histone chaperone, Proc. Natl. Acad. Sci. U.S.A., 2014, vol. 111, no. 35, pp. 12752–12757.CrossRefGoogle Scholar

Copyright information

© Allerton Press, Inc. 2019

Authors and Affiliations

  • N. V. Malyuchenko
    • 1
    Email author
  • E. Yu. Kotova
    • 2
  • M. P. Kirpichnikov
    • 1
    • 3
  • V. M. Studitsky
    • 1
    • 2
  • A. V. Feofanov
    • 1
    • 3
  1. 1.Bioengineering Department, Biological Faculty, Moscow State UniversityMoscowRussia
  2. 2.Cancer Epigenetics Team, Fox Chase Cancer CenterPhiladelphiaUnited States
  3. 3.Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesMoscowRussia

Personalised recommendations