Atm-, p53-, and Gadd45a-deficient mice show an increased frequency of homologous recombination at different stages during development.
Atm, p53, and Gadd45a form part of a DNA-damage cellular response pathway; the absence of any one of these components results in increased genomic instability. We conducted an in vivo examination of the frequency of spontaneous homologous recombination in Atm-, p53-, or Gadd45a-deficient mice. In the absence of p53, we observed the greatest increase in events, a lesser increase in the absence of Atm, and only a modest increase in the absence of Gadd45a. The striking observation was the difference in the time at which the spontaneous events occurred in atm and trp53 mutant mice. The frequency of homologous recombination in atm mutant mice was increased later during development. In contrast, p53 appears to have a role in suppressing homologous recombination early during development, when p53 is known to spontaneously promote p21 activity. The timing of the increased spontaneous recombination was similar in the Gadd45a- and p53-deficient mice. This temporal resolution suggests that Atm and p53 can act to maintain genomic integrity by different mechanisms in certain in vivo contexts.
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005127:Eye Color / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics; D025521:Tumor Suppressor Proteins; D000097642:GADD45 Proteins
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C499072:Gadd45a protein, mouse; D000097642:GADD45 Proteins; C576325:Atm protein, mouse