Advertisement

Biochemistry (Moscow)

, Volume 74, Issue 1, pp 92–96 | Cite as

Replication protein A modulates the activity of human telomerase in vitro

  • M. P. Rubtsova
  • D. A. Skvortsov
  • I. O. Petruseva
  • O. I. Lavrik
  • P. V. Spirin
  • V. S. Prasolov
  • F. L. Kisseljov
  • O. A. Dontsova
Article

Abstract

Our aim was to investigate how replication protein A (RPA) in a wide range of concentration can regulate the activity of human telomerase. We used an in vitro system based on human cell extracts with or without RPA. It has been shown that removal of RPA leads to loss of telomerase activity and addition of RPA restores telomerase activity and at the same time promotes telomerase processivity. However, high excess of RPA inhibited telomerase processivity and caused the synthesis of relatively short DNA fragments (about 50–100 nucleotides). We assume that, together with other telomere-binding proteins, RPA may take part in activation of telomere overhang elongation by telomerase at a certain stage of a cell cycle as well as in regulation of telomere length.

Key words

telomerase RPA telomeres regulation 

Abbreviations

nt

nucleotides

RPA

replication protein A

SSB

single-strand binding protein

ssDNA

single-strand DNA

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Iftod, C., Daniely, Y., and Borowiec, J. A. (1999) Crit. Rev. Biochem. Mol. Biol., 34, 141–180.CrossRefGoogle Scholar
  2. 2.
    Fanning, E., Klimovich, V., and Nager, A. R. (2006) Nucleic Acids Res., 34, 4126–4137.PubMedCrossRefGoogle Scholar
  3. 3.
    Lavrik, O. I., Kolpashchikov, D. M., Weisshart, K., Nasheuer, H. P., Khodyreva, S. N., and Favre, A. (1999) Nucleic Acids Res., 27, 4235–4240.PubMedCrossRefGoogle Scholar
  4. 4.
    Maga, G., Frouin, I., Spadari, S., and Hubscher, U. (2001) J. Biol. Chem., 276, 18235–18242.PubMedCrossRefGoogle Scholar
  5. 5.
    Schramke, V., Luciano, P., Brevet, V., Guillot, S., Corda, Y., Longhese, M. P., Gilson, E., and Geli, V. (2004) Nat. Genet., 36, 46–54.PubMedCrossRefGoogle Scholar
  6. 6.
    Salas, T. R., Petruseva, I., Lavrik, O., Bourdoncle, A., Mergny, J. L., Favre, A., and Saintome, C. (2006) Nucleic Acids Res., 34, 4857–4865.PubMedCrossRefGoogle Scholar
  7. 7.
    Kibe, T., Ono, Y., Sato, K., and Ueno, M. (2007) Mol. Biol. Cell., 18, 2378–2387.PubMedCrossRefGoogle Scholar
  8. 8.
    Neto, J. L., Lira, C. B., Giardini, M. A., Khater, L., Perez, A. M., Peroni, L. A., dos Reis, J. R., Freitas-Junior, L. H., Ramos, C. H., and Cano, M. I. (2007) Biochem. Biophys. Res. Commun., 358, 417–423.PubMedCrossRefGoogle Scholar
  9. 9.
    Cohen, S., Jacob, E., and Manor, H. (2004) Biochim. Biophys. Acta, 1679, 129–140.PubMedCrossRefGoogle Scholar
  10. 10.
    Counter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., and Bacchetti, S. (1992) EMBO J., 11, 1921–1929.PubMedGoogle Scholar
  11. 11.
    Henricksen, L. A., Umbricht, C. B., and Wold, M. S. (1994) J. Biol. Chem., 269, 11121–11132.PubMedGoogle Scholar
  12. 12.
    Perrault, R., Cheong, N., Wang, H., Wang, H., and Iliakis, G. (2001) Int. J. Radiat. Biol., 77, 593–607.PubMedCrossRefGoogle Scholar
  13. 13.
    Petruseva, I. O., Tikhanovich, I. S., Chelobanov, B. P., and Lavrik, O. I. (2008) J. Mol. Recogn., 21, 154–162.CrossRefGoogle Scholar
  14. 14.
    Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., and Shay, J. W. (1994) Science, 266, 2011–2015.PubMedCrossRefGoogle Scholar
  15. 15.
    Kim, N. W., and Wu, F. (1997) Nucleic Acids Res., 25, 2595–2597.PubMedCrossRefGoogle Scholar
  16. 16.
    Meyer, R. R., and Laine, P. S. (1990) Microbiol. Rev., 54, 342–380.PubMedGoogle Scholar
  17. 17.
    Smogorzewska, A., and de Lange, T. (2004) Annu. Rev. Biochem., 73, 177–208.PubMedCrossRefGoogle Scholar
  18. 18.
    Wang, F., Podell, E. R., Zaug, A. J., Yang, Y., Baciu, P., Cech, T. R., and Lei, M. (2007) Nature, 445, 506–510.PubMedCrossRefGoogle Scholar
  19. 19.
    Loayza, D., and de Lange, T. (2003) Nature, 423, 1013–1018.PubMedCrossRefGoogle Scholar
  20. 20.
    Paeschke, K., Juranek, S., Simonsson, T., Hempel, A., Rhodes, D., and Lipps, H. J. (2008) Nat. Struct. Mol. Biol., 15, 598–604.PubMedCrossRefGoogle Scholar
  21. 21.
    Arthanari, H., and Bolton, P. H. (2001) Chem. Biol., 8, 221–230.PubMedCrossRefGoogle Scholar
  22. 22.
    Sabourin, M., Tuzon, C. T., and Zakian, V. A. (2007) Mol. Cell, 27, 550–561.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2009

Authors and Affiliations

  • M. P. Rubtsova
    • 1
  • D. A. Skvortsov
    • 1
  • I. O. Petruseva
    • 2
  • O. I. Lavrik
    • 2
  • P. V. Spirin
    • 3
  • V. S. Prasolov
    • 3
  • F. L. Kisseljov
    • 4
  • O. A. Dontsova
    • 1
  1. 1.Chemical FacultyLomonosov Moscow State UniversityMoscowRussia
  2. 2.Institute of Chemical Biology and Fundamental MedicineSiberian Division of the Russian Academy of SciencesNovosibirskRussia
  3. 3.Institute of Molecular BiologyRussian Academy of SciencesMoscowRussia
  4. 4.Blokhin Cancer Research CenterRussian Academy of Medical SciencesMoscowRussia

Personalised recommendations