Mammalian X-ray-sensitive mutants which are defective in non-homologous (illegitimate) DNA double-strand break repair

Biochimie. Jan-Feb 1999;81(1-2):107-16. doi: 10.1016/s0300-9084(99)80043-1.

Abstract

In all organisms multiple pathways to repair DNA double-strand breaks (DSB) have been identified. In mammalian cells DSB are repaired by two distinct pathways, homologous and non-homologous (illegitimate) recombination. X-ray-sensitive mutants have provided a tool for the identification and understanding of the illegitimate recombination pathway in mammalian cells. Two (sub-)pathways can be distinguished, the first mediated by DNA-PK-dependent protein kinase (DNA-PK), and the second directed by the hMre11/hRad50 complex. A variety of mutants impaired in DSB repair by illegitimate recombination, with mutations in Ku, DNA-PKcs, XRCC4 or nibrin, have been described. Herein, the characterization of these mutants with respect to the impaired cellular function and the molecular defect is provided. Further studies on these mutants, as well as on new mutants impaired in as-of-yet unidentified pathways, should be helpful to a better understanding of DSB repair and of the processes leading to genome instability and cancer.

Publication types

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

MeSH terms

  • Animals
  • DNA Damage*
  • DNA Repair*
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins*
  • Endodeoxyribonucleases*
  • Exodeoxyribonucleases*
  • Fungal Proteins / metabolism
  • Mammals
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Saccharomyces cerevisiae Proteins*

Substances

  • DNA-Binding Proteins
  • Fungal Proteins
  • RAD50 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • DNA-Activated Protein Kinase
  • Protein-Serine-Threonine Kinases
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae