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Role of Oxidation of XRCC1 Protein in Regulation of Mammalian DNA Repair Process

  • BIOCHEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
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Abstract

The influence of XRCC1 protein oxidation on the modification of proteins catalyzed by poly(ADP-ribose)polymerases (PARP1 and PARP2) was studied for the first time. XRCC1, PARP1, and PARP2, functioning as scaffold proteins, are responsible for coordination of multistep repair of most abundant DNA lesions. We showed that the XRCC1 oxidation reduces the efficiency of its ADP-ribosylation and the protein affinity for poly(ADP-ribose). The ADP-ribose modification of various XRCC1 forms is enhanced in the presence of DNA polymerase β (Polβ), capable of forming a stable complex with XRCC1. Oxidation suppresses the inhibitory effect of XRCC1 and its complex with Polβ on the automodification of PARP1 and PARP2, which may enhance the efficiency of repair. The results of this study indicate that the oxidation of XRCC1 plays a role in fine regulation of poly(ADP-ribosyl)ation levels of proteins and their coordinating functions in DNA repair.

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REFERENCES

  1. Abbotts, R. and Wilson, D.M., 3rd, Coordination of DNA single strand break repair, Free Radic. Biol. Med., 2017, vol. 107, pp. 228–244. https://doi.org/10.1016/j.freeradbiomed.2016.11.039

    Article  CAS  PubMed  Google Scholar 

  2. Moor, N.A. and Lavrik, O.I., Protein–protein interactions in DNA base excision repair, Biochemistry (Moscow), 2018, vol. 83, no. 4, pp. 411–422.

    CAS  PubMed  Google Scholar 

  3. London, R.E., The structural basis of XRCC1-mediated DNA repair, DNA Repair (Amst.), 2015, vol. 30, pp. 90–103. https://doi.org/10.1016/j.dnarep.2015.02.005

    Article  CAS  Google Scholar 

  4. Horton, J.K., Stefanick, D.F., Gassman, N.R., et al., Preventing oxidation of cellular XRCC1 affects PARP-mediated DNA damage responses, DNA Repair (Amst.), 2013, vol. 12, no. 9, pp. 774–785. https://doi.org/10.1016/j.dnarep.2013.06.004

    Article  CAS  Google Scholar 

  5. Horton, J.K., Seddon, H.J., Zhao, M.L., et al., Role of the oxidized form of XRCC1 in protection against extreme oxidative stress, Free Radic. Biol. Med., 2017, vol. 107, pp. 292–300. https://doi.org/10.1016/j.freeradbiomed.2017.02.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Masson, M., Niedergang, C., Schreiber, V., et al., XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage, Mol. Cell Biol., 1998, vol. 18, pp. 3563–3571. https://doi.org/10.1128/mcb.18.6.3563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ohashi, Y., Itaya, A., Tanaka, Y., et al., Poly(ADP-ribosyl)ation of DNA polymerase β in vitro, Biochem. Biophys. Res. Commun., 1986, vol. 140, no. 2, pp. 666–673. https://doi.org/10.1016/0006-291x(86)90783-7

    Article  CAS  PubMed  Google Scholar 

  8. Moor, N.A., Vasil’eva, I.A., Anarbaev, R.O., et al., Quantitative characterization of protein–protein complexes involved in base excision DNA repair, Nucleic Acids Res., 2015, vol. 43, pp. 6009–6022. https://doi.org/10.1093/nar/gkv569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Belousova, E.A., Vasil’eva, I.A., Moor, N.A., et al., Clustered DNA lesions containing 5-formyluracil and AP site: repair via the BER system, PLoS One, 2013, vol. 8. e68576. https://doi.org/10.1371/journal.pone.0068576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kumar, A., Widen, S.G., Williams, K.R., et al., Studies of the domain structure of mammalian DNA polymerase β. Identification of a discrete template binding domain, J. Biol. Chem., 1990, vol. 265, no. 4, pp. 2124–2131.

    CAS  PubMed  Google Scholar 

  11. Vasil’eva, I.A., Anarbaev, R.O., Moor, N.A., et al., Dynamic light scattering study of base excision DNA repair proteins and their complexes, Biochim. Biophys. Acta, Proteins Proteom., 2019, vol. 1867, no. 3, pp. 297–305. https://doi.org/10.1016/j.bbapap.2018.10.009

    Article  CAS  Google Scholar 

  12. Alvarez-Gonzalez, R. and Jacobson, M.K., Characterization of polymers of adenosine diphosphate ribose generated in vitro and in vivo, Biochemistry, 1987, vol. 26, no. 11, pp. 3218–3224. https://doi.org/10.1021/bi00385a042

    Article  CAS  PubMed  Google Scholar 

  13. Chim, N., Harmston, C.A., Guzman, D.J., et al., Structural and biochemical characterization of the essential DsbA-like disulfide bond forming protein from mycobacterium tuberculosis, BMC Struct. Biol., 2013, vol. 13, p. 23. https://doi.org/10.1186/1472-6807-13-23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wunderlich, M. and Glockshuber, R., Redox properties of protein disulfide isomerase (DsbA) from Escherichia coli,Protein Sci., 1993, vol. 2, no. 5, pp. 717–726. https://doi.org/10.1002/pro.5560020503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Polo, L.M., Xu, Y., Hornyak, P., et al., Efficient single-strand break repair requires binding to both poly(ADP-ribose) and DNA by the central BRCT domain of XRCC1, Cell Rep., 2019, vol. 26, no. 3, pp. 573–581. e5. https://doi.org/10.1016/j.celrep.2018.12.082

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Funding

This work was supported by the Russian Science Foundation (project no. 19-14-00107).

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Correspondence to O. I. Lavrik.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

AUTHOR CONTRIBUTIONSI

Vasil'eva and N. A. Moor contributed equally to this work.

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Translated by M. Batrukova

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Vasil’eva, I.A., Moor, N.A. & Lavrik, O.I. Role of Oxidation of XRCC1 Protein in Regulation of Mammalian DNA Repair Process. Dokl Biochem Biophys 489, 357–361 (2019). https://doi.org/10.1134/S1607672919060012

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  • DOI: https://doi.org/10.1134/S1607672919060012

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