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Transcription, topoisomerases and recombination

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Abstract

Transcription, DNA topoisomerases and genetic recombination are interrelated for several structural reasons. Transcription can affect DNA topology, resulting in effects on recombination. It can also affect the chromatin structure in which the DNA resides. Topoisomerases can affect DNA and/or chromatin structure influencing the recombination potential at a given site. Here we briefly review the extent to which homologous direct repeat recombination and site-specific recombination in eukaryotes are affected by transcription and topoisomerases. In some cases, transcription or the absence of topoisomerases have little or no effect on recombination. In others, they are important components in the recombinational process. The common denominator of any effects of transcription and topoisomerases on recombination is their shared role in altering DNA topology.

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References

  1. Alt, F. W., Blackwell, T. K., and Yancopoulos, G. D., Development of the primary antibody repertoire. Science238 (1987) 1079.

    Article  CAS  PubMed  Google Scholar 

  2. Bailis, A. M., Arthur, L., and Rothstein, R., Genome rearrangement intop3 mutants ofSaccharomyces cerevisiae requires a functionalRAD1 excision repair gene. Molec. cell. Biol.12 (1992) 4988–4993.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Bailis, A. M., and Rothstein, R., A defect in mismatch repair inSaccharomyces cerevisiae stimulates ectopic recombination between homologous genes by an excision repair dependent process. Genetics126 (1990) 535–547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Boeke, J., Lacroute, F., and Fink, G., A positive selection for mutants lacking orotidine-5′-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Molec. gen. Genet.197 (1984) 342–346.

    Article  Google Scholar 

  5. Brewer, B. J., Lockson, D., and Fangman, W. L., The arrest of replication forks in the rDNA of yeast occurs independently of transcription. Cell71 (1992) 267–276.

    Article  CAS  PubMed  Google Scholar 

  6. Brill, S. J., DiNardo, S., Voelkel-Meiman, K., and Sternglanz, R., Need for DNA topoisomerase activity as a swivel for DNA replication for transcription of ribosomal DNA. Nature326 (1987) 414–416.

    Article  CAS  PubMed  Google Scholar 

  7. Brill, S. J., and Sternglanz, R., Transcription-dependent DNA supercoiling in yeast DNA topoisomerase mutants. Cell54 (1988) 403–411.

    Article  CAS  PubMed  Google Scholar 

  8. Bullock, P., Miller, J., and Botchan, M., Effects of poly [d(pGpT).d(pApC)] and poly [d(pCpG).d(pCpG)] repeats on homologous recombination in somatic cells. Molec. cell. Biol.6 (1986) 3948–3953.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Capone, M., Watrin, F., Fernex, C., Horvat, B., Krippl, B., Wu, L., Scollay, R., and Ferrier, P., TCRb and TCRa gene enhancers confer tissue- and stage-specificity to V(D)J recombination events. EMBO J.12 (1993) p. 4335–4346.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chen, J., Troustine, M., Alt, F. W., Young, F., Kuhara, J. F., Loring, J. F., and Huszar, D., Immunoglobulin gene rear-rangement in B cell deficient mice generated by targeted deletion of the JH locus. Int. Immun.5 (1993) 647–656.

    Article  CAS  PubMed  Google Scholar 

  11. Christman, M. F., Dietrich, F. S., and Fink, G. R., Mitotic recombination in the rDNA ofSaccharomyces cerevisiae is suppressed by the combined action of DNA topoisomerases I and II. Cell55 (1988) 413–425.

    Article  CAS  PubMed  Google Scholar 

  12. Cosloy, S. D., Effect of transcription of RecBC- and RecF-mediated recombination within the tryptophan operon ofEscherichia coli K12. J. Bact.139 (1979) 1079–1081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Davies, R. W., Dove, W. F., Inokuchi, H., Lehman, J. F., and Roehrdanz, R. L., Regulation of λ prophage excision by the transcriptional state of the DNA. Nature New Biol.238 (1972) 43–45.

    Article  CAS  PubMed  Google Scholar 

  14. Drexler, H., Transduction of Gal+ by coliphage T1. I. Role of hybrids of bacterial and prophage λ deoxyribonucleic acid. J. Virol.9 (1972) 273–279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Drexler, H., Transduction of Gal+ by coliphage T1. II. Role of λ transcription control in the efficiency of transduction. J. Virol.9 (1972) 280–285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Drlica, K., Bacterial topoisomerases and the control of DNA supercoiling. Trends Genet.6 (1990) 433–437.

    Article  CAS  PubMed  Google Scholar 

  17. Engler, P., Roth, P., Kim, J. Y., and Storb, U., Factors affecting the rearrangement efficiency of an Ig test gene. J. Immun.146 (1991) 2826–2835.

    Article  CAS  PubMed  Google Scholar 

  18. Engler, P., Weng, A., and Storb, U., Influence of CpG methylation and target spacing on V(D)J recombination in a transgenic substrate. Molec. cell. Biol.13 (1993) 571–577.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Ennis, D. G., Amunsen, S. K., and Smith, G. R., Genetic functions promoting homologous recombination inEscherichia coli: a study of inversions in phage lambda. Genetics115 (1987) 11–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gallant, J., and Spottswood, T., The recombinogenic effect of thymidylate starvation inEscherichia coli merodiploids. Genetics52 (1967) 107–118.

    Article  Google Scholar 

  21. Gallant, J., and Walker, C., Thymidylate starvation and recombination inEscherichia coli. Genetics56 (1967) 561.

    Google Scholar 

  22. Giaever, G. N., and Wang, J. C., Supercoiling of intracellular DNA can occur in eukaryotic cells. Cell55 (1988) 849–856.

    Article  CAS  PubMed  Google Scholar 

  23. Gottesman, S., and Gottesman, M. E., Elements involved in site-specific recombination in bacteriophage lambda. J. molec. Biol.91 (1975) 489–499.

    Article  CAS  PubMed  Google Scholar 

  24. Gritzmaker, C. A., Molecular Aspects of Heavy-Chain Class Switching. Critical Rev. Immun.9 (1989) 173–200.

    Google Scholar 

  25. Gu, H., Zou, Y.-R., and Rajewsky, K., Independent Control of Immunoglobulin Switch Recombination at Individual Switch Regions Evidenced through Cre-loxP-Mediated Gene Targeting. Cell73 (1993) 1155–1164.

    Article  CAS  PubMed  Google Scholar 

  26. Haber, J. E., Mating-type gene switching inSaccharomyces cerevisiae. Trends Genet.8 (1992) 446–452.

    Article  CAS  PubMed  Google Scholar 

  27. Herman, R. K., Effect of gene induction on frequency of intragenic recombination of chromosome and F-merogenote inEscherichia coli K12. Genetics58 (1967) 55–67.

    Article  Google Scholar 

  28. Herman, R. K., Transcription and intragenic recombination in polar mutants ofEscherichia coli. Science120 (1968) 782–783.

    Article  Google Scholar 

  29. Herskowitz, I., Rine, J., and Strathern, J., Mating-type determination and mating-type interconversion inSaacharomyces cerevisiae, in: The molecular and cellular biology of the yeastSaccharomyces cerevisiae: Gene expression. Vol. 2, pp. 583–657. Eds J. R. Broach, J. R. Pringle and E. W. Jones. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York 1992.

    Google Scholar 

  30. Holm, C., Stearn, T., and Botstein, D., DNA topoisomerase II must act at mitosis to prevent nondisjunction and chromosome breakage. Molec. cell. Biol.9 (1989) 159–168.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Honigberg, S. M., and Radding, C. M., The mechanics of winding and unwinding helices in recombination: torsional stress associated with strand transfer promoted by RecA protein. Cell54 (1988) 525–532.

    Article  CAS  PubMed  Google Scholar 

  32. Hsieh, C., and Lieber, M. R., CpG methylated minichromosomes become inaccessible for V(D)J recombination after undergoing replication. EMBO J.11 (1992) 315–325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hsieh, C., McCloskey, R. P., and Lieber, M. R., V(D)J recombination on minichromosomes is not affected by transcription. J. biol. Chem.267 (1992) 5613–5619.

    Article  Google Scholar 

  34. Ikeda, H., Aoki, K., and Naito, A., Illegitimate recombination mediated in vitro by DNA gyrase ofEscherichia coli: Structure of recombinant DNA molecules. Proc. natl Acad. Sci. USA79 (1982) 3724–3728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ikeda, H., and Kobayashi, I., Involvement of DNA-dependent RNA polymerase in a RecA-independent pathway of genetic recombination inEscherichia coli. Proc. natl Acad. Sci. USA74 (1977) 3932–3936.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ikeda, H., and Matsumoto, T., Transcription promotes recA-independent recombination mediated by DNA-dependent RNA polymerase inEscherichia coli. Proc. natl Acad. Sci. USA76 (1979) 4571–4575.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Inokuchi, H., and Dove, W. F., Physical studies of RNA involvement in bacteriophage λ DNA replication and prophage excision. J. molec. Biol.74 (1973) 721–727.

    Article  CAS  PubMed  Google Scholar 

  38. Jenuwein, T., Forrester, W., Qiu, R.-G., and Grosschedl, R., The immunoglobulin mu enhancer core establishes local factor access in nuclear chromatin independent of transcriptional stimulation. Genes & Dev.7 (1993) 2016–2032.

    Article  CAS  Google Scholar 

  39. Keil, R. L., and Roeder, S. G., Cis-acting, recombination-stimulating activity in a fragment of the ribosomal DNA ofSaccharomyces cerevisiae. Cell39 (1984) 377–386.

    Article  CAS  PubMed  Google Scholar 

  40. Kim, R. A., and Wang, J. C., A subthreshold of DNA topoisomerases leads to the excision of yeast rDNA as extrachromosomal rings. Cell57 (1989) 975–985.

    Article  CAS  PubMed  Google Scholar 

  41. Kim, R. A., and Wang, J. C., Identification of the yeastTOP3 gene product as a single-strand specific DNA topoisomerase. J. biol. Chem.267 (1992) 17178–17185.

    Article  CAS  PubMed  Google Scholar 

  42. Kmiec, E. B., and Holloman, W. K., Homologous pairing of DNA molecules byUstilago recl protein is promoted by sequences of Z-DNA. Cell44 (1986) 545–554.

    Article  CAS  PubMed  Google Scholar 

  43. Knab, A. M., Fertala, J., and Bjornsti, M.-A., Mechanisms of camptothecin resistance in yeast DNA topoisomerase I mutants. J. biol. Chem.268 (1993) 22322–22330.

    Article  CAS  PubMed  Google Scholar 

  44. Levin, N. A., Bjornsti, M.-A., and Fink, G. R., A novel mutation in DNA topoisomerase I of yeast causes DNA damage andRAD9-dependent cell cycle arrest. Genetics133 (1993) 799–814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lieber, M. R., Site-specific recombination in the immune system. FASEB J.5 (1991) 2934–2944.

    Article  CAS  PubMed  Google Scholar 

  46. Lin, Y.-H., and Keil, R. L., Mutations affecting RNA polymerase I-stimulated exchange and rDNA recombination in yeast. Genetics127 (1991) 31–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Liu, L. F., and Wang, J. C., Supercoiling of the DNA template during transcription. Proc. natl Acad. Sci. USA84 (1987) 7024–7027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Liu, L. H., DNA topoisomerase poisons as antitumor drugs. A. Rev. Biochem.58 (1989) 351–375.

    Article  CAS  Google Scholar 

  49. Liu, L. H., Anticancer drugs that convert DNA topoisomerases into DNA damaging agents, in: DNA topology and its biological effects. pp. 371–389. Eds N. R. Cozzarelli and J. C. Wang, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 1990.

    Google Scholar 

  50. Lutzker, S., and Alt, F., Structure and expression of germ line immunoglobulin g2b transcripts. Molec. cell. Biol.8 (1988) 1849–1852.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Merino, A., Madden, K. R., Lane, W. S., Champoux, J. J., and Reinberg, D., DNA topoisomerase I is involved in both repression and activation of transcription. Nature365 (1993) 227–232.

    Article  CAS  PubMed  Google Scholar 

  52. Millington-Ward, A. M., Recombination and transcription in theHISB andPABA1 loci ofAspergillus nidulans. Genetica41 (1970) 557–574.

    Article  CAS  PubMed  Google Scholar 

  53. Morse, R. H., Transcribed chromatin. Trends biochem. Sci.17 (1992) 23–26.

    Article  CAS  PubMed  Google Scholar 

  54. Nasmyth, K. A., The regulation of yeast mating-type chromatin structure bySIR: an action at a distance affecting both transcription and transposition. Cell30 (1982) 567–578.

    Article  CAS  PubMed  Google Scholar 

  55. Nitiss, J., and Wang, J. C., DNA topoisomerase-targeting antitumor drugs can be studied in yeast. Proc. natl. Acad. Sci. USA85 (1988) 7501–7505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Nitiss, J. L., Liu, Y.-X., and Hsiung, Y., A temperature sensitive topoisomerase II allele confers temperature dependent drug resistance on amsacrine and ectoposide: a genetic system for determining the targets of topoisomerase II inhibitors. Cancer Res.53 (1993) 89–93.

    CAS  PubMed  Google Scholar 

  57. Oakes, M., Nogi, Y., Clark, M. W. and Nomura, M., Structural alterations of the nucleolus in mutants ofSaccharomyces cerevisiae defective in RNA polymerase I. Molec. cell. Biol.13 (1993) 2441–2455.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Pruss, G. J., and Drlica, K., DNA supercoiling and prokaryotic transcription. Cell56 (1989) 521–523.

    Article  CAS  PubMed  Google Scholar 

  59. Reaban, M. E., and Griffin, J. A., Induction of RNA-stabilized DNA conformers by transcription of an immunoglobulin switch region. Nature348 (1990) 342–344.

    Article  CAS  PubMed  Google Scholar 

  60. Reeder, R. H., rRNA synthesis in the nucleolus. Trends Genet.6 (1990) 390–395.

    Article  CAS  PubMed  Google Scholar 

  61. Rothstein, R., Helms, C., and Rosenberg, N., Concerted deletions and inversions are caused by mitotic recombination between delta sequences inSaccharomyces cerevisiae. Molec. cell. Biol.7 (1987) 1198–1207.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Schofield, M. A., Agbunag, R., Michaels, M. L., and Miller, J. H., Cloning and sequencing ofEscherichia coli mutR shows its identity totopB, encoding topoisomerase III. J. Bact.174 (1992) 5168–5170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Schultz, M. C., Brill, S. J., Sternglantz, R., and Reeder, R. H., Topoisomerases and yeast rRNA transcription: negative supercoiling stimulates initiation and topoisomerase activity is required for elongation. Genes and Dev.6 (1992) 1332–1341.

    Article  CAS  PubMed  Google Scholar 

  64. Shestakov, S., and Barbour, S., The relationship between recombination and transcription of the lactose genes ofEscherichia coli K12. Genetics57 (1967) 283–289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Stavnezer, J., Radcliffe, G., Lin, Y.-C., Nietupski, J., Berggren, L., Sitia, R., and Severinson, E., Immunoglobulin heavy-chain switching may be directed by prior induction of transcripts from constant-region genes. Proc. natl Acad. Sci. USA85 (1988) 7704–7708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Thomas, B. J., and Rothstein, R., Elevated recombination rates in transcriptionally active DNA. Cell56 (1989) 619–630.

    Article  CAS  PubMed  Google Scholar 

  67. Treco, D., and Arnheim, N., The evolutionary conserved repetitive sequence d(TG.AC)n promotes reciprocal exchange and generates unusual recombinant tetrads during. Molec. cell. Biol.6 (1986) 3934–3947.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Voelkel-Meiman, K., Keil, R. L., and Roeder, S. G., Recombination-stimulating sequences in yeast ribosomal DNA correspond to sequences regulating transcription by RNA polymerase I. Cell48 (1987) 1071–1079.

    Article  CAS  PubMed  Google Scholar 

  69. Voelkel-Meiman, K., and Roeder, S. G., A chromosome containingHOT1 preferentially receives information during mitotic interchromosomal gene conversion. Genetics124 (1990) 561–572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Wallis, J. W., Chrebet, G., Brodsky, G., Rolfe, M., and Rothstein, R., A hyper-recombination mutation inSaccharomyces cerevisiae identifies a novel eukaryotic topoisomerase. Cell58 (1989) 409–419.

    Article  CAS  PubMed  Google Scholar 

  71. Wang, J. C., DNA topoisomerases. A. Rev. Biochem.54 (1985) 665–697.

    Article  CAS  Google Scholar 

  72. Whoriskey, S. K., Schofield, M. A., and Miller, J. H., Isolation and characterization ofEscherichia coli mutants with altered rates of deletion formation. Genetics127 (1991) 21–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Xu, L., Gorham, B., Li, S., Bottaro, A., Alt, F. W., and Rothman, P., Replacement of germ-line epsilon promoter by gene targeting alters control of immunoglobulin heavy chain class switching. Proc. natl Acad. Sci. USA90 (1993) 3705–3709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Genetics & Development, College of Physicians & Surgeons, Columbia University, 701 West 168th Street, 10032, New York, New York, USA

    S. Gangloff & R. Rothstein

  2. Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, 94305-5324, Stanford, California, USA

    M. R. Lieber

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Gangloff, S., Lieber, M.R. & Rothstein, R. Transcription, topoisomerases and recombination. Experientia 50, 261–269 (1994). https://doi.org/10.1007/BF01924009

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