Single-strand break repair and genetic disease

Nat Rev Genet. 2008 Aug;9(8):619-31. doi: 10.1038/nrg2380.


Hereditary defects in the repair of DNA damage are implicated in a variety of diseases, many of which are typified by neurological dysfunction and/or increased genetic instability and cancer. Of the different types of DNA damage that arise in cells, single-strand breaks (SSBs) are the most common, arising at a frequency of tens of thousands per cell per day from direct attack by intracellular metabolites and from spontaneous DNA decay. Here, the molecular mechanisms and organization of the DNA-repair pathways that remove SSBs are reviewed and the connection between defects in these pathways and hereditary neurodegenerative disease are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apraxias / genetics
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Chromosomes
  • DNA Breaks, Double-Stranded
  • DNA Breaks, Single-Stranded*
  • DNA Repair / genetics
  • DNA Repair / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Genetic Diseases, Inborn / genetics*
  • Humans
  • Models, Biological
  • Neoplasms / genetics
  • Nerve Degeneration / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology
  • Oculomotor Nerve Diseases / genetics
  • Phosphoric Diester Hydrolases / genetics
  • Phosphoric Diester Hydrolases / physiology
  • Spinocerebellar Ataxias / genetics


  • APTX protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Phosphoric Diester Hydrolases
  • TDP1 protein, human