Accuracy and Ageing

  • Robin Holliday
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 40)


It is taken for granted that present day organisms have a variety of devices to ensure that macromolecules are made accurately and also that, in the case of DNA, structural integrity is maintained by elaborate repair mechanisms. Yet this cannot always have been the case, since primitive organisms must have been far less accurate. Increased accuracy and repair would confer a selective advantage, leading eventually by evolution to the situation we now observe. However, the avoidance or elimination of errors requires the consumption of metabolic energy. This is well known in the case of DNA synthesis, where errors can be removed by a proof-reading exonuclease mechanism, and each wrong nucleoside triphosphate is converted to a monophosphate. The synthesis of repair enzymes is also energy-consuming. Less is known about the mechanisms which ensure accurate protein synthesis, but it is likely that ribosomes and associated factors not only allow the assembly of polypeptide chains, but also effectively discriminate against the incorporation of wrong amino acids, perhaps by a kinetic proof reading mechanism or its equivalent (1,2). Another way of increasing accuracy is to reduce the rate of synthesis of macromolecules, since this allows more time for the dissociation of incorrect substrate-enzyme complexes (3). There is evidence that mutations in ribosomal proteins which increase accuracy also reduce the rate of translation (4). There is also much evidence that when defective proteins are synthesised, they are preferentially degraded (5,6).


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  1. 1.
    J.J. Hopfield, Proc. Nat. Acad. Sci. U.S.A. 71: 4135 (1974)Google Scholar
  2. 2.
    A.B. Caplan and J.R. Menninger, J. Mol. Biol. 134: 621 (1979)CrossRefGoogle Scholar
  3. 3.
    J. Ninio, Biochemie, 57: 587 (1975)CrossRefGoogle Scholar
  4. 4.
    D.J. Galas and E.W. Branscomb, Nature, London. 262: 617 (1976)CrossRefGoogle Scholar
  5. 5.
    A.L. Goldberg and J.F. Dice, Biochem. Rev. 43: 835 (1974)CrossRefGoogle Scholar
  6. 6.
    A.L. Goldberg and A.C. St. John, Biochem. Rev. 45: 747 (1976)CrossRefGoogle Scholar
  7. 7.
    L.E. Orgel, Proc. Nat. Acad. Sci. U.S.A. 49: 517 (1963)CrossRefGoogle Scholar
  8. 8.
    L.E. Orgel, Proc. Nat. Acad. Sci. U.S.A. 67: 1476 (1973)CrossRefGoogle Scholar
  9. 9.
    T.B.L. Kirkwood, J. Theoret. Biol. 82: 363 (1980)CrossRefGoogle Scholar
  10. 10.
    C.M. Lewis and R. Holliday, Nature, London. 228: 877 (1970)CrossRefGoogle Scholar
  11. 11.
    E.W. Branscomb and D.J. Galas, Nature, London. 254: 161 (1975)CrossRefGoogle Scholar
  12. 12.
    R.F. Rosenberger, G. Foskett and R. Holliday, Mech. Age. Devel. (in press)Google Scholar
  13. 13.
    T.B.L. Kirkwood, Nature, London. 270: 301 (1977)Google Scholar
  14. 14.
    T.B.L. Kirkwood and R. Holliday, Proc. Roy. Soc., London B. 205: 531 (1979)CrossRefGoogle Scholar
  15. 15.
    R. Dawkins in The Selfish Gene, Oxford University Press (1976)Google Scholar
  16. 16.
    P.B. Medawar, in An Unsolved Problem in Biology, H.K. Lewis, London. (1952)Google Scholar
  17. 17.
    L. Hayflick and P.S. Moorhead, Exp. Cell Res. 25: 585 (1961)CrossRefGoogle Scholar
  18. 18.
    G.M. Martin, C.A. Sprague and C.J. Epstein, Lab. Invest. 23: 86 (1970)PubMedGoogle Scholar
  19. 19.
    J.D. Buchanan and A. Stevens, Mech. Age. Deve). 7: 321 (1978)CrossRefGoogle Scholar
  20. S. Linn, M.V. Kairis and R. Holliday, Proc. Nat. Acad. Sci., U.S.A. 73: 2818 (1976)Google Scholar
  21. 21.
    V. Murray, Changes in DNA polymerase during ageing, PhD. thesis Council for National Academic Awards, U.K. (1979) and in preparation.Google Scholar
  22. 22.
    J.F. Speyer, J.D. Karam and A.B. Lenny, Cold Spr. Herb. Symp. Quant. Biol. 31: 693 (1966)CrossRefGoogle Scholar
  23. 23.
    S. Fulder and R. Holliday, Cell 6: 67 (1975)CrossRefGoogle Scholar
  24. 24.
    S. Fulder, Mech. Age. Devel. 10: 101 (1979)CrossRefGoogle Scholar
  25. 25.
    A. Morley, S.A. Cox and R. Holliday (submitted for publication)Google Scholar
  26. 26.
    G.H. Strauss and R.J. Albertini, Mut. Res. 61: 353 (1979)CrossRefGoogle Scholar
  27. 27.
    L. Szilard, Proc. Nat. Acad. Sci., U.S.A. 45: 30 (1959)CrossRefGoogle Scholar
  28. 28.
    L. Hayflick, Exp. Cell Res. 37: 614 (1965)CrossRefGoogle Scholar
  29. 29.
    T.B.L. Kirkwood and R. Holliday in Structural Pathology of DNA and the Biology of Ageing, L. Schoeller, ed.,Freiburg Deutsche Forschungsgemeinschaft (in press)Google Scholar
  30. 30.
    L.L. Cavalli-Sforza and W.F. Bodmer, in The Genetics of Human Populations, W.H. Freeman, San Francisco (1971)Google Scholar
  31. 31.
    R. DeMars, Radiation Res. 24: 335 (1974)Google Scholar
  32. 32.
    V.J. Cristofalo and B.B. Sharf, Exp. Cell Res. 76: 419 (1973)CrossRefGoogle Scholar
  33. 33.
    R.A. Vincent and P.C. Huang, Exp. Cell Res. 102: 31 (1976)CrossRefGoogle Scholar
  34. 34.
    R. Holliday, L.I. Huschtscha and T.B.L. Kirkwood (in preparation)Google Scholar
  35. 35.
    K.V.A. Thompson and R. Holliday, Exp. Cell Res. 112: 281 (1978)CrossRefGoogle Scholar
  36. 36.
    H. Hoehn, E.M. Bryant, P. Johnston, T.H. Norwood and G.M. Martin, Nature, London. 258: 608 (1975)CrossRefGoogle Scholar
  37. 37.
    L.E. Orgel, Nature, London. 243: 441 (1973)CrossRefGoogle Scholar
  38. 38.
    R. Holliday and G.M. Tarrant, Nature, London. 238: 26 (1972)CrossRefGoogle Scholar
  39. 39.
    T.B.L. Kirkwood and R. Holliday, J. Mol. Biol. 97: 257 (1975)CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Robin Holliday
    • 1
  1. 1.National Institute for Medical ResearchMill Hill, LondonUK

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