Genomic integrity and the repair of double-strand DNA breaks

A Pastink1, J C Eeken, P H Lohman

  • 1Sylvius Laboratory, Department of Radiation Genetics and Chemical Mutagenesis, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands. a.pastink@lumc.nl

Mutation Research
|August 17, 2001
PubMed

Insights

DNA double-strand breaks (DSBs) threaten genome integrity. This review details conserved repair pathways like homologous recombination (HR) and non-homologous end joining (NHEJ), crucial for preventing cancer.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • DNA double-strand breaks (DSBs) pose a significant threat to genome integrity.
  • Unrepaired or misrepaired DSBs can lead to chromosomal aberrations and are linked to cancer development in mammals.

Purpose of the Study:

  • To review current knowledge on DNA double-strand break repair mechanisms.
  • To highlight recent advancements in understanding the biochemical functions of proteins involved in DSB repair.

Main Methods:

  • Literature review of DNA repair pathways.
  • Focus on homologous recombination (HR), non-homologous end joining (NHEJ), and single-strand annealing (SSA).
  • Comparative analysis across different organisms and cell cycle stages.

Main Results:

  • DSB repair mechanisms are conserved in eukaryotes but vary in relative importance.
  • HR is primary in yeast, while both HR and NHEJ are critical in higher eukaryotes.
  • Defects in HR or NHEJ in mammals increase cancer predisposition and chromosomal aberrations.

Conclusions:

  • Multiple pathways, including HR and NHEJ, maintain genome integrity by repairing DSBs.
  • Understanding the precise biochemical activities of repair proteins is key to comprehending these processes.
  • Dysfunctional DSB repair is a significant factor in tumorigenesis.

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