DNA ligase I deficiency in Bloom's syndrome

Abstract

Certain rare human diseases with autosomal recessive mode of inheritance are associated with a greatly increased cancer frequency which may reflect specific defects in DNA repair or replication. These disorders include xeroderma pigmentosum, ataxia-telangiectasia, Fanconi's anaemia and Bloom's syndrome1. Cells from individuals with Bloom's syndrome2 usually grow slowly in culture and exhibit increased chromosomal breakage and rearrangement, an elevated frequency of sister chromatid exchanges, retarded rates of progression of DNA replication forks, delayed conversion of replication intermediates to high-molecular-weight DNA, and slightly increased sensitivity to DNA-damaging agents3–11. Several of these features are also characteristic of Escherichia coli and yeast mutants with a defective DNA ligase12–22. In this investigation we show that one of the two DNA ligases of human cells, ligase I, is defective in a representative lymphoid cell line of Bloom's syndrome origin.

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References

  1. 1

    Friedberg, E. C. DNA Repair, 505–574 (Freeman, New York, 1985).

    Google Scholar 

  2. 2

    German, J., Bloom, D. & Passarge, E. Clin. Genet 25, 166–174 (1984).

    CAS  Article  Google Scholar 

  3. 3

    German, J., Archibald, R. & Bloom, D. Science 148, 506–507 (1965).

    ADS  CAS  Article  Google Scholar 

  4. 4

    Chaganti, R. S. K., Schonberg, S. & German, J. Proc. natn. Acad. Sci. U.S.A. 71, 4508–4512 (1974).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Hand, R. & German, J. Proc. natn. Acad. Sd U.S.A. 72, 758–762 (1975).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Krepinsky, A. B., Heddle, J. A. & German, J. Hum. Genet. 50, 151–156 (1979).

    CAS  Article  Google Scholar 

  7. 7

    Giannelli, F., Benson, P. F., Pawsey, S. A. & Polani, P. E. Nature 265, 466–469 (1977).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Kapp, L. N. Biochim. biophys. Acta 696, 226–227 (1982).

    CAS  Article  Google Scholar 

  9. 9

    Ockey, C. H. & Saffhill, R. Carcinogenesis 7, 53–57 (1986).

    CAS  Article  Google Scholar 

  10. 10

    Zbinden, I. & Cerutti, P. Biochem. biophys. Res. Commun. 98, 579–587 (1981).

    CAS  Article  Google Scholar 

  11. 11

    Aurias, A. et al. Cancer Genet Cytogenet. 16, 131–136 (1985).

    CAS  Article  Google Scholar 

  12. 12

    Gellert, M. & Bullock, M. L. Proc. natn. Acad. Sci. U.S.A. 67, 1580–1587 (1970).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Gottesman, M. M., Hicks, M. L. & Gellert, M. J. molec. Biol. 77, 531–547 (1973).

    CAS  Article  Google Scholar 

  14. 14

    Pauling, C. & Hamm, L. Proc. natn. Acad. Sci. U.S.A. 64, 1195–1202 (1969).

    ADS  CAS  Article  Google Scholar 

  15. 15

    Morse, L. S. & Pauling, C. Proc. natn. Acad. Sci. U.S.A. 72, 4645–4649 (1975).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Konrad, E. B., Modrich, P. & Lehman, I. R. J. molec. Biol. 77, 519–529 (1973).

    CAS  Article  Google Scholar 

  17. 17

    Konrad, E. B. J. Bact. 130, 167–172 (1977).

    CAS  PubMed  Google Scholar 

  18. 18

    Nasmyth, K. A. Cell 12, 1109–1120 (1977).

    CAS  Article  Google Scholar 

  19. 19

    Nasmyth, K. A. J. molec. Biol. 130, 273–284 (1979).

    CAS  Article  Google Scholar 

  20. 20

    Johnston, L. H. & Nasmyth, K. A. Nature 274, 891–893 (1978).

    ADS  CAS  Article  Google Scholar 

  21. 21

    Moore, C. W. J. Bact. 150, 1227–1233 (1982).

    CAS  PubMed  Google Scholar 

  22. 22

    Barker, D. G., Johnson, A. L. & Johnston, L. H. Molec. gen. Genet. 200, 458–462 (1985).

    CAS  Article  Google Scholar 

  23. 23

    Soderhall, S. & Lindahl, T. J. biol. Chem. 250, 8438–8444 (1975).

    CAS  PubMed  Google Scholar 

  24. 24

    Soderhall, S. & Lindahl, T. FEBS Lett. 67, 1–8 (1976).

    CAS  Article  Google Scholar 

  25. 25

    Soderhall, S. Nature 260, 640–642 (1976).

    ADS  CAS  Article  Google Scholar 

  26. 26

    Teraoka, H. & Tsukada, K. J. biol. Chem. 260, 2937–2940 (1985).

    CAS  PubMed  Google Scholar 

  27. 27

    Teraoka, H., Sumikawa, T. & Tsukada, K. J. biol. Chem. 261, 6888–6892 (1986).

    CAS  PubMed  Google Scholar 

  28. 28

    Chan, J. Y. H. & Becker, F. F. Carcinogenesis 6, 1275–1277 (1985).

    CAS  Article  Google Scholar 

  29. 29

    Arrand, J. E., Willis, A. E., Goldsmith, I. & Lindahl, T. J. biol. Chem. 261, 9079–9082 (1986).

    CAS  PubMed  Google Scholar 

  30. 30

    Olivera, B. M. & Lehman, I. R. Proc. natn. Acad. Sci. U.S.A. 57, 1426–1433 (1967).

    ADS  CAS  Article  Google Scholar 

  31. 31

    Chan, J. Y. H., Becker, F. F., German, J. & Ray, J. H. Nature (in the press).

  32. 32

    Hashimoto, T. et al. Basic Life Sci. 29, 765–774 (1984).

    PubMed  Google Scholar 

  33. 33

    Shiraishi, Y., Yosida, T. H. & Sandberg, A. A. Proc. natn. Acad. Sci. U.S.A. 82, 5102–5106 (1985).

    ADS  CAS  Article  Google Scholar 

  34. 34

    Brothman, A. R., Scott Cram, L., Bartholdi, M. F. & Kraemer, P. M. Cancer Res. 46, 791–797 (1986).

    CAS  PubMed  Google Scholar 

  35. 35

    Kenne, K. & Ljungquist, S. Nucleic Acids Res. 12, 3057–3068 (1984).

    CAS  Article  Google Scholar 

  36. 36

    Parker, V. P. & Lieberman, M. W. Nucleic Acids Res. 4, 2029–2037 (1977).

    CAS  Article  Google Scholar 

  37. 37

    Spanos, A., Holliday, R. & German, J. Hum. Genet. 73, 119–122 (1986).

    CAS  Article  Google Scholar 

  38. 38

    Emerit, I. & Cerutti, P. Proc. natn. Acad. Sci. U.S.A. 78, 1868–1872 (1981).

    ADS  CAS  Article  Google Scholar 

  39. 39

    Bamezai, R. & Shiraishi, Y. Exp. Cell Res. 164, 163–173 (1986).

    CAS  Article  Google Scholar 

  40. 40

    Gupta, P. K. & Sirover, M. A. Proc. natn. Acad. Sci. U.S.A. 81, 757–761 (1984).

    ADS  CAS  Article  Google Scholar 

  41. 41

    Kim, S. et al. Mutat. Res. 173, 141–145 (1986).

    CAS  Article  Google Scholar 

  42. 42

    Dehazya, P. & Sirover, M. A. Cancer Res. 46, 3756–3761 (1986).

    CAS  PubMed  Google Scholar 

  43. 43

    Alberts, B. & Herrick, G. Meth. Enzym. 21D, 198–217 (1971).

    Article  Google Scholar 

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Willis, A., Lindahl, T. DNA ligase I deficiency in Bloom's syndrome. Nature 325, 355–357 (1987). https://doi.org/10.1038/325355a0

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