Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1997 May;17(5):2624–2630. doi: 10.1128/mcb.17.5.2624

Accessibility to topoisomerases I and II regulates the replication efficiency of simian virus 40 minichromosomes.

L Halmer 1, C Gruss 1
PMCID: PMC232112  PMID: 9111332

Abstract

We determined the effects of chromatin structure on template accessibility to replication factors and used three different templates as substrates for simian virus 40 (SV40) DNA replication in vitro: native and salt-treated SV40 minichromosomes and protein-free SV40 DNA. Native minichromosomes contain histone H1 and numerous nonhistone proteins in addition to the core histones, whereas salt-treated minichromosomes carry essentially only core histones. We reasoned that the less densely packed salt-treated minichromosomes should be more effective replication templates due to their more extended configuration. However, contrary to this expectation, we found that native minichromosomes replicated with significantly higher efficiency than salt-treated minichromosomes, while protein-free DNA was most active as a replication template. The higher replication efficiency of native minichromosomes was due to two activities bound to the chromatin, which were identified as DNA topoisomerases I and II. By using chromatin substrates of different general configurations, we also showed that the overall chromatin structure determines accessibility to topoisomerases I and II and thereby the efficiency of replicative chain elongation.

Full Text

The Full Text of this article is available as a PDF (2.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Avemann K., Knippers R., Koller T., Sogo J. M. Camptothecin, a specific inhibitor of type I DNA topoisomerase, induces DNA breakage at replication forks. Mol Cell Biol. 1988 Aug;8(8):3026–3034. doi: 10.1128/mcb.8.8.3026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Champoux J. J. Topoisomerase I is preferentially associated with isolated replicating simian virus 40 molecules after treatment of infected cells with camptothecin. J Virol. 1988 Oct;62(10):3675–3683. doi: 10.1128/jvi.62.10.3675-3683.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Champoux J. J. Topoisomerase I is preferentially associated with normal SV40 replicative intermediates, but is associated with both replicating and nonreplicating SV40 DNAs which are deficient in histones. Nucleic Acids Res. 1992 Jul 11;20(13):3347–3352. doi: 10.1093/nar/20.13.3347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cheng L., Kelly T. J. Transcriptional activator nuclear factor I stimulates the replication of SV40 minichromosomes in vivo and in vitro. Cell. 1989 Nov 3;59(3):541–551. doi: 10.1016/0092-8674(89)90037-8. [DOI] [PubMed] [Google Scholar]
  5. Crippa M. P., Trieschmann L., Alfonso P. J., Wolffe A. P., Bustin M. Deposition of chromosomal protein HMG-17 during replication affects the nucleosomal ladder and transcriptional potential of nascent chromatin. EMBO J. 1993 Oct;12(10):3855–3864. doi: 10.1002/j.1460-2075.1993.tb06064.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Csordas A. On the biological role of histone acetylation. Biochem J. 1990 Jan 1;265(1):23–38. doi: 10.1042/bj2650023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davie J. R., Hendzel M. J. Multiple functions of dynamic histone acetylation. J Cell Biochem. 1994 May;55(1):98–105. doi: 10.1002/jcb.240550112. [DOI] [PubMed] [Google Scholar]
  8. Ding H. F., Rimsky S., Batson S. C., Bustin M., Hansen U. Stimulation of RNA polymerase II elongation by chromosomal protein HMG-14. Science. 1994 Aug 5;265(5173):796–799. doi: 10.1126/science.8047885. [DOI] [PubMed] [Google Scholar]
  9. Dröge P. Protein tracking-induced supercoiling of DNA: a tool to regulate DNA transactions in vivo? Bioessays. 1994 Feb;16(2):91–99. doi: 10.1002/bies.950160205. [DOI] [PubMed] [Google Scholar]
  10. Fanning E., Knippers R. Structure and function of simian virus 40 large tumor antigen. Annu Rev Biochem. 1992;61:55–85. doi: 10.1146/annurev.bi.61.070192.000415. [DOI] [PubMed] [Google Scholar]
  11. Fletcher T. M., Hansen J. C. Core histone tail domains mediate oligonucleosome folding and nucleosomal DNA organization through distinct molecular mechanisms. J Biol Chem. 1995 Oct 27;270(43):25359–25362. doi: 10.1074/jbc.270.43.25359. [DOI] [PubMed] [Google Scholar]
  12. Gruss C., Knippers R. Structure of replicating chromatin. Prog Nucleic Acid Res Mol Biol. 1996;52:337–365. doi: 10.1016/s0079-6603(08)60971-x. [DOI] [PubMed] [Google Scholar]
  13. Gruss C., Wu J., Koller T., Sogo J. M. Disruption of the nucleosomes at the replication fork. EMBO J. 1993 Dec;12(12):4533–4545. doi: 10.1002/j.1460-2075.1993.tb06142.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Halmer L., Gruss C. Effects of cell cycle dependent histone H1 phosphorylation on chromatin structure and chromatin replication. Nucleic Acids Res. 1996 Apr 15;24(8):1420–1427. doi: 10.1093/nar/24.8.1420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Halmer L., Gruss C. Influence of histone H1 on the in vitro replication of DNA and chromatin. Nucleic Acids Res. 1995 Mar 11;23(5):773–778. doi: 10.1093/nar/23.5.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hsiang Y. H., Hertzberg R., Hecht S., Liu L. F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem. 1985 Nov 25;260(27):14873–14878. [PubMed] [Google Scholar]
  17. Ishimi Y., Sugasawa K., Hanaoka F., Eki T., Hurwitz J. Topoisomerase II plays an essential role as a swivelase in the late stage of SV40 chromosome replication in vitro. J Biol Chem. 1992 Jan 5;267(1):462–466. [PubMed] [Google Scholar]
  18. Jakobovits E. B., Bratosin S., Aloni Y. A nucleosome-free region in SV40 minichromosomes. Nature. 1980 May 22;285(5762):263–265. doi: 10.1038/285263a0. [DOI] [PubMed] [Google Scholar]
  19. Kaufman P. D., Kobayashi R., Kessler N., Stillman B. The p150 and p60 subunits of chromatin assembly factor I: a molecular link between newly synthesized histones and DNA replication. Cell. 1995 Jun 30;81(7):1105–1114. doi: 10.1016/s0092-8674(05)80015-7. [DOI] [PubMed] [Google Scholar]
  20. Kingston R. E., Bunker C. A., Imbalzano A. N. Repression and activation by multiprotein complexes that alter chromatin structure. Genes Dev. 1996 Apr 15;10(8):905–920. doi: 10.1101/gad.10.8.905. [DOI] [PubMed] [Google Scholar]
  21. Krude T., Knippers R. Transfer of nucleosomes from parental to replicated chromatin. Mol Cell Biol. 1991 Dec;11(12):6257–6267. doi: 10.1128/mcb.11.12.6257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Krude T., de Maddalena C., Knippers R. A nucleosome assembly factor is a constituent of simian virus 40 minichromosomes. Mol Cell Biol. 1993 Feb;13(2):1059–1068. doi: 10.1128/mcb.13.2.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  24. Liu L. F., Wang J. C. Supercoiling of the DNA template during transcription. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7024–7027. doi: 10.1073/pnas.84.20.7024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Loidl P. Histone acetylation: facts and questions. Chromosoma. 1994 Dec;103(7):441–449. doi: 10.1007/BF00337382. [DOI] [PubMed] [Google Scholar]
  26. Madden K. R., Stewart L., Champoux J. J. Preferential binding of human topoisomerase I to superhelical DNA. EMBO J. 1995 Nov 1;14(21):5399–5409. doi: 10.1002/j.1460-2075.1995.tb00224.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Müller U., Zentgraf H., Eicken I., Keller W. Higher order structure of simian virus 40 chromatin. Science. 1978 Aug 4;201(4354):406–415. doi: 10.1126/science.208155. [DOI] [PubMed] [Google Scholar]
  28. Nelson E. M., Tewey K. M., Liu L. F. Mechanism of antitumor drug action: poisoning of mammalian DNA topoisomerase II on DNA by 4'-(9-acridinylamino)-methanesulfon-m-anisidide. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1361–1365. doi: 10.1073/pnas.81.5.1361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Quintini G., Treuner K., Gruss C., Knippers R. Role of amino-terminal histone domains in chromatin replication. Mol Cell Biol. 1996 Jun;16(6):2888–2897. doi: 10.1128/mcb.16.6.2888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rainwater R., Mann K. Association of topoisomerases I and II with the chromatin in SV40-infected monkey cells. Virology. 1991 Mar;181(1):408–411. doi: 10.1016/0042-6822(91)90515-d. [DOI] [PubMed] [Google Scholar]
  31. Saragosti S., Moyne G., Yaniv M. Absence of nucleosomes in a fraction of SV40 chromatin between the origin of replication and the region coding for the late leader RNA. Cell. 1980 May;20(1):65–73. doi: 10.1016/0092-8674(80)90235-4. [DOI] [PubMed] [Google Scholar]
  32. Simanis V., Lane D. P. An immunoaffinity purification procedure for SV40 large T antigen. Virology. 1985 Jul 15;144(1):88–100. doi: 10.1016/0042-6822(85)90308-3. [DOI] [PubMed] [Google Scholar]
  33. Smith S., Stillman B. Purification and characterization of CAF-I, a human cell factor required for chromatin assembly during DNA replication in vitro. Cell. 1989 Jul 14;58(1):15–25. doi: 10.1016/0092-8674(89)90398-x. [DOI] [PubMed] [Google Scholar]
  34. Smith S., Stillman B. Stepwise assembly of chromatin during DNA replication in vitro. EMBO J. 1991 Apr;10(4):971–980. doi: 10.1002/j.1460-2075.1991.tb08031.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sogo J. M., Stahl H., Koller T., Knippers R. Structure of replicating simian virus 40 minichromosomes. The replication fork, core histone segregation and terminal structures. J Mol Biol. 1986 May 5;189(1):189–204. doi: 10.1016/0022-2836(86)90390-6. [DOI] [PubMed] [Google Scholar]
  36. Stillman B. W., Gluzman Y. Replication and supercoiling of simian virus 40 DNA in cell extracts from human cells. Mol Cell Biol. 1985 Aug;5(8):2051–2060. doi: 10.1128/mcb.5.8.2051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Travers A. A. Chromatin structure and dynamics. Bioessays. 1994 Sep;16(9):657–662. doi: 10.1002/bies.950160911. [DOI] [PubMed] [Google Scholar]
  38. Trieschmann L., Alfonso P. J., Crippa M. P., Wolffe A. P., Bustin M. Incorporation of chromosomal proteins HMG-14/HMG-17 into nascent nucleosomes induces an extended chromatin conformation and enhances the utilization of active transcription complexes. EMBO J. 1995 Apr 3;14(7):1478–1489. doi: 10.1002/j.1460-2075.1995.tb07134.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Turner B. M., O'Neill L. P. Histone acetylation in chromatin and chromosomes. Semin Cell Biol. 1995 Aug;6(4):229–236. doi: 10.1006/scel.1995.0031. [DOI] [PubMed] [Google Scholar]
  40. Wang J. C. DNA topoisomerases. Annu Rev Biochem. 1985;54:665–697. doi: 10.1146/annurev.bi.54.070185.003313. [DOI] [PubMed] [Google Scholar]
  41. Wang J. C. DNA topoisomerases: why so many? J Biol Chem. 1991 Apr 15;266(11):6659–6662. [PubMed] [Google Scholar]
  42. Wang Z., Dröge P. Differential control of transcription-induced and overall DNA supercoiling by eukaryotic topoisomerases in vitro. EMBO J. 1996 Feb 1;15(3):581–589. [PMC free article] [PubMed] [Google Scholar]
  43. Yang L., Jessee C. B., Lau K., Zhang H., Liu L. F. Template supercoiling during ATP-dependent DNA helix tracking: studies with simian virus 40 large tumor antigen. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6121–6125. doi: 10.1073/pnas.86.16.6121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yang L., Wold M. S., Li J. J., Kelly T. J., Liu L. F. Roles of DNA topoisomerases in simian virus 40 DNA replication in vitro. Proc Natl Acad Sci U S A. 1987 Feb;84(4):950–954. doi: 10.1073/pnas.84.4.950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Zechiedrich E. L., Osheroff N. Eukaryotic topoisomerases recognize nucleic acid topology by preferentially interacting with DNA crossovers. EMBO J. 1990 Dec;9(13):4555–4562. doi: 10.1002/j.1460-2075.1990.tb07908.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES