DNA Joining in Mammalian Cells

  1. T. Lindahl*,
  2. C. Prigent*,
  3. D.E. Barnes*,
  4. A.R. Lehmann,
  5. M.S. Satoh*,
  6. E. Roberts*,
  7. R.A. Nash*,
  8. P. Robins*, and
  9. G. Daly*
  1. Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Herts, EN6 3LD United Kingdom; MRC Cell Mutation Unit, University of Sussex, Brighton, Sussex BN1 9RR, United Kingdom

This extract was created in the absence of an abstract.

Excerpt

Since their discovery almost 30 years ago, DNA ligases have been used extensively as reagent enzymes. Joining of DNA single-strand breaks and double-strand breaks can be achieved efficiently by employing overproduced microbial DNA ligases, and this is a key step in recombinant DNA research. The facile sealing of DNA strand interruptions with commercially obtained enzymes in vitro may have generated the impression that DNA ligation is a simple, unregulated process in vivo. This is not likely to be the case. Instead, recent work on DNA-joining activities in mammalian cell nuclei indicates that DNA ligation efficiency is regulated at several levels, including transcriptional and posttranslational control of DNA ligase activity, and is influenced by the occurrence of separate protein activators and inhibitors of DNA ligases, the presence of multiple DNA ligases in cell nuclei, and the existence of other proteins such as poly(ADP-ribose) polymerase that bind tightly at DNA chain breaks....

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