Association of p53 and MSH2 with recombinative repair complexes during S phase.
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.
Zink
Daniele
D
Institut für Anthropologie und Humangenetik LMU München, Goethestr. 31,80336 München, Germany.
Mayr
Christoph
C
Janz
Christine
C
Wiesmüller
Lisa
L
D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D016193:G1 Phase; D005720:Gamma Rays; D046911:Macromolecular Substances; D008938:Mitosis; D051718:MutS Homolog 2 Protein; D009692:Nucleic Acid Heteroduplexes / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D011995:Recombination, Genetic; D016196:S Phase; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism* / Q000502:physiology
D019313:BRCA1 Protein; D002843:Chromatin; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009692:Nucleic Acid Heteroduplexes; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D051718:MutS Homolog 2 Protein