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Recognition and processing of damaged DNA

T Lindahl1

  • 1Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire, UK.

Journal of Cell Science. Supplement
|January 1, 1995
PubMed
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Mammalian DNA repair pathways, particularly base excision-repair, are well-studied. However, key proteins involved in DNA strand break response, like poly(ADP-ribose) polymerase and multiple DNA ligases, differ significantly from yeast, suggesting distinct eukaryotic repair mechanisms.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Base excision-repair corrects DNA damage from hydrolysis, oxidation, and alkylation.
  • Mammalian DNA replication and repair enzymes often have yeast counterparts.
  • Significant differences exist in DNA strand break response pathways between eukaryotes.

Purpose of the Study:

  • To review mammalian DNA repair factors, focusing on base excision-repair.
  • To highlight current uncertainties in mammalian DNA repair mechanisms.
  • To compare DNA strand break responses in mammals versus yeast.

Main Methods:

  • Literature review of mammalian DNA repair pathways.
  • Comparison of identified mammalian nuclear proteins with their yeast counterparts.

Related Experiment Videos

  • Identification of DNA ligase families in human cell nuclei.

    • Main Results:

    • Most DNA replication/repair enzymes (e.g., DNA polymerases) are conserved between mammals and yeast.
    • Key mammalian proteins binding DNA strand interruptions, such as poly(ADP-ribose) polymerase and DNA-dependent protein kinase, are absent in yeast.
    • Mammalian nuclei contain four distinct DNA ligases, unlike the single DNA ligase found in yeast.
    • The p53 protein, elevated by DNA strand breaks in mammals, is not detected in yeast.

    Conclusions:

    • Mammalian DNA repair pathways exhibit significant divergence from those in lower eukaryotes, especially concerning DNA strand break responses.
    • The presence of multiple DNA ligases and specific binding proteins in mammals suggests a more complex DNA repair machinery compared to yeast.
    • Further research is needed to elucidate the functional implications of these differences in eukaryotic DNA repair.