p53 is dispensable for UV-induced cell cycle arrest at late G(1) in mammalian cells.
Genotoxic agents, including gamma-rays and UV light, induce transient arrest at different phases of the cell cycle. These arrests are required for efficient repair of DNA lesions, and employ several factors, including the product of the tumor suppressor gene p53 that plays a central role in the cellular response to DNA damage. p53 protein has a major function in the gamma-ray-induced cell cycle delay in G(1) phase. However, it remains uncertain as to whether p53 is also involved in the UV-mediated G(1) delay. This report provides evidence that p53 is not involved in UV-induced cellular growth arrest in late G(1) phase. This has been demonstrated in HeLa cells synchronized at the G(1)/S border by aphidicolin, followed by UV exposure. Interestingly, the length of this p53-independent G(1) arrest has been shown to be UV dose-dependent. Similar results were also obtained with other p53-deficient cell lines, including human promyelocytic leukemia HL-60 and mouse p53 knock-out cells. As expected, all of these cell lines were defective in gamma-ray-induced cell growth arrest at late G(1). Moreover, it is shown that in addition to cell cycle arrest, HL-60 cells undergo apoptosis in G(1) phase in response to UV light but not to gamma-rays. Together, these findings indicate that p53- compromised cells have a differential response following exposure to ionizing radiation or UV light.
Al-Mohanna
M A
MA
King Faisal Specialist Hospital and Research Center, Biological and Medical Research Department, MBC No. 03, PO Box 3354, Riyadh 11211, Saudi Arabia.
Al-Khodairy
F M
FM
Krezolek
Z
Z
Bertilsson
P A
PA
Al-Houssein
K A
KA
Aboussekhra
A
A
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects*; D002460:Cell Line; D053938:DNA Fragmentation; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D016193:G1 Phase / Q000528:radiation effects*; D005720:Gamma Rays; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D008027:Light; D051379:Mice; D018345:Mice, Knockout; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014466:Ultraviolet Rays
D016159:Tumor Suppressor Protein p53