p53 is involved in clearance of ionizing radiation-induced RAD51 foci in a human colon cancer cell line.
We have investigated p53-related differences in cellular response to DNA damaging agents, focusing on p53s effects on RAD51 protein level and sub-cellular localization post exposure to ionizing radiation. In a human colon cancer cell line, HCT116 and its isogenic p53-/- subcell line we show here p53-independent RAD51 foci formation but interestingly the resolution of RAD51 foci showed clear p53 dependence. In p53 wt cells, but not in p53-/- cells, RAD51 protein level decreased 48 h post irradiation and fluorescence immunostaining showed resolution of RAD51 foci and relocalization of RAD51 to nucleoli at time points corresponding to the decrease in RAD51 protein level. Both cell lines rejoined DNA double strand breaks efficiently with similar kinetics and p53 status did not influence sensitivity to DNA damaging agents. We suggest that p53 has a role in RAD51 clearance post DSB repair and that nucleoli might be sites of RAD51 protein degradation.
Orre
Lukas M
LM
Cancer Centrum Karolinska Institutet, Department of Oncology and Pathology, Division of Medical Radiation Biology, Stockholm, Sweden. Lukas.Orre@ki.se
Stenerlöw
Bo
B
Dhar
Sumeer
S
Larsson
Rolf
R
Lewensohn
Rolf
R
Lehtiö
Janne
J
D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D051135:Rad51 Recombinase / Q000378:metabolism*; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D051135:Rad51 Recombinase