title: Radiation-induced cellular senescence results from a slippage of long-term G2 arrested cells into G1 phase.
abstract: Diploid cells undergoing senescence and mitotic slippage have been reported in the literature. However, the mechanisms triggering senescence in long-term G2-arrested cells are currently unclear. Previously, we reported that the cell cycle of the human uveal melanoma cell line, 92-1, is suspended for up to 6 d upon exposure to 10 Gy ionizing radiation (IR), followed by senescence. In the current study, we initially distinguished senescence in long-term blocked 92-1 cells from mitotic slippage by confirming the blockage of cells in the G2 phase. We subsequently showed that the genes essential for G2-M transition are prematurely downregulated at both the transcriptional and translational levels. Furthermore, levels of the G1-specific markers, Cyclin D1 and Caveolin-1, were distinctly increased, while S/G2-specific markers, Cyclin B1 and Aurora A, were significantly downregulated. These findings collectively imply that long-term G2-arrested cells undergo senescence via G2 slippage. To our knowledge, this is the first study to report that the cellular process of G2 slippage is the mechanism responsible for senescence of cells under long-term G2 arrest.
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modem Physics, Chinese Academy of Sciences, Lanzhou, China.
authors.forename: Caiyong
authors.initials: C
authors.lastname: Ye
authors.forename: Xurui
authors.initials: X
authors.lastname: Zhang
authors.forename: Jianghua
authors.initials: J
authors.lastname: Wan
authors.forename: Lei
authors.initials: L
authors.lastname: Chang
authors.forename: Wentao
authors.initials: W
authors.lastname: Hu
authors.forename: Zhitong
authors.initials: Z
authors.lastname: Bing
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Junhong
authors.initials: J
authors.lastname: Li
authors.forename: Jinpeng
authors.initials: J
authors.lastname: He
authors.forename: Jufang
authors.initials: J
authors.lastname: Wang
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhou
mesh_terms: D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000235:genetics / Q000528:radiation effects*; D015536:Down-Regulation / Q000235:genetics / Q000528:radiation effects; D016193:G1 Phase / Q000235:genetics / Q000528:radiation effects*; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D008938:Mitosis / Q000235:genetics / Q000528:radiation effects; D011839:Radiation, Ionizing; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects; D018709:Statistics, Nonparametric; D013997:Time Factors; D014965:X-Rays
chemical_list: D051880:Receptors, Notch
keywords: DNA damage response; G2 slippage; cell cycle checkpoint; ionizing radiation; mitotic slippage; senescence