Radiation-induced senescence-like growth arrest requires TP53 function but not telomere shortening.
Suzuki, K., Mori, I., Nakayama, Y., Miyakoda, M., Kodama, S. and Watanabe, M. Radiation-Induced Senescence-like Growth Arrest Requires TP53 Function but not Telomere Shortening. Normal human diploid cells irradiated with X rays showed permanent cell cycle arrest and exhibited senescence-like phenotypes including the expression of senescence-associated beta-galactosidase (SA-beta-gal). X irradiation caused persistent phosphorylation of TP53 at Ser 15 and accumulation of the TP53 protein, followed by the induction of CDKN1A (also known as p21(Waf1/Cip1)) and CDKN2A (also known as p16), preceded the expression of SA-beta-gal. NCI-H1299 human lung carcinoma cells, in which no TP53 protein was expressed, were irradiated with X rays with or without the exogenous expression of TP53 gene. Although induction of TP53 protein alone could induce SA-beta-gal expression, the frequency of SA-beta-gal-positive cells was significantly increased when TP53-induced H1299 cells were exposed to X rays. The mean terminal restriction fragment length in normal human cells was approximately 12 kb and did not change in SA-beta-gal-positive cells. These results indicate that ionizing radiation induces senescence-like growth arrest that is dependent on TP53 function but independent of telomere shortening. Our findings suggest that cells harboring irreparable DNA damage are programmed to undergo premature senescence to maintain the integrity of the genome.
Suzuki
K
K
Laboratory of Radiation and Life Science, Department of Health Sciences, School of Pharmaceutical Sciences, Nagasaki University, Nagasaki 852-8521, Japan.
Mori
I
I
Nakayama
Y
Y
Miyakoda
M
M
Kodama
S
S
Watanabe
M
M
D002453:Cell Cycle / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology / Q000528:radiation effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D004790:Enzyme Induction; D006801:Humans; D010766:Phosphorylation / Q000528:radiation effects; D016615:Telomere / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D001616:beta-Galactosidase