Association of p53 and MSH2 with recombinative repair complexes during S phase

Oncogene. 2002 Jul 18;21(31):4788-800. doi: 10.1038/sj.onc.1205614.


Our previous recombination and biochemical analyses have led to the hypothesis that the tumor suppressor p53 monitors homologous recombination, a function which was previously attributed to the mismatch repair protein MSH2. Here, we show that a certain fraction of p53 is concentrated within discrete nuclear foci of cells synchronized in G1 phase, a pattern which becomes even more pronounced in S phase, especially after gamma-ray treatment. p53 foci show some colocalization with MSH2 within distinct foci during G1 phase, while dots formed by BRCA1 display an independent localization pattern. In S phase nuclei, p53 foci almost completely colocalize with MSH2 foci and associate with the recombination surveillance factor BRCA1 in irradiated S phase cells. These p53 and MSH2 foci also show significant overlaps with foci of the recombination enzymes Rad50 and Rad51, which for the first time unveiled recombination-related functions of p53 in replicating cells. During S phase, p53 and MSH2 are maximally active in binding to early recombination intermediates, and coexist within the same nuclear DNA-protein complexes. Our data suggest that p53 is linked similarly to homologous recombination as MSH2 and provide further evidence for the new concept of a dual role of p53 in the regulation of growth and repair.

Publication types

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

MeSH terms

  • Animals
  • BRCA1 Protein / metabolism
  • Cell Division
  • Cell Line
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism
  • Chromatin / metabolism
  • DNA Repair*
  • DNA-Binding Proteins / metabolism
  • G1 Phase
  • Gamma Rays
  • Macromolecular Substances
  • Mitosis
  • MutS Homolog 2 Protein
  • Nucleic Acid Heteroduplexes / metabolism
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / physiology
  • Recombination, Genetic
  • S Phase
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Protein p53 / physiology


  • BRCA1 Protein
  • Chromatin
  • DNA-Binding Proteins
  • Macromolecular Substances
  • Nucleic Acid Heteroduplexes
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53
  • MutS Homolog 2 Protein