Increased UV-induced SCEs but normal repair of DNA damage in p53-deficient mouse cells.
UV-induced sister chromatid exchanges (SCEs) in p53-deficient mouse cells were studied to obtain more evidence regarding the involvement of p53 protein in the DNA repair pathway as a checkpoint protein. After 5 J/m2 UV irradiation, mutant-type homozygous cells for p53-deficiency showed the same number of SCEs as the heterozygous and wild-type homozygous cells. In the heterozygous and wild-type homozygous cells, no further increase of SCEs was observed after 10 J/m2 UV irradiation. In contrast, in mutant-type homozygous cells about twice as many SCEs were induced by 10 J/m2 UV as by 5 J/m2 UV. In mutant-type homozygous cells, fractions of S-phase cells decreased just after 10 J/m2 UV irradiation, but recovered to higher than control levels within a short time, while in heterozygous and wild-type homozygous cells, the decrease in S-phase cells was prolonged by more than 6 hr and no increase above control levels was observed. Although no difference in UV sensitivity and repair of UV-induced DNA damage was found among the 3 genotypes, which were determined by the relative colony-forming ability after UV irradiation and removal of thymine dimers and (6-4) photoproducts from cellular DNA, our data strongly suggest an impaired checkpoint function in p53-deficient cells when DNA is damaged.
Radiation Biology Center, Kyoto University, Japan.
K
K
Ishizaki
Y
Y
Ejima
T
T
Matsunaga
R
R
Hara
A
A
Sakamoto
M
M
Ikenaga
Y
Y
Ikawa
S
S
Aizawa
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D005434:Flow Cytometry; D006579:Heterozygote; D051379:Mice; D016196:S Phase / Q000528:radiation effects; D012854:Sister Chromatid Exchange / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000502:physiology; D014466:Ultraviolet Rays / Q000009:adverse effects*
D016159:Tumor Suppressor Protein p53