p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis

doi:10.3967/bes2016.064

	p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis
	Zhang Xu Rui 1,2; Liu Yong Ai 1,2; Sun Fang 1,2; Li He1,2 ; Lei Su Wen 3; Wang Ju Fang 1
刊名	BIOMEDICAL AND ENVIRONMENTAL SCIENCES
	2016-07-01
卷号	29 页码:484-493
关键词	G2/M transition DNA damage Ionizing radiation G2 arrest
ISSN号	0895-3988
DOI	10.3967/bes2016.064
英文摘要	Objective To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest. Methods Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation. Depletion of p21 was carried out by employing the siRNA technique. Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28, an M-phase marker. Senescence was assessed by senescence-associated-beta-galactosidase (SA-beta-gal) staining combined with Ki67 staining, a cell proliferation marker. Results Accompanying increased p21, the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays. Furthermore, these irradiated cells were blocked at the G2 phase followed by cellular senescence. Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases, as well as the high expression of histone H3 phosphorylated at Ser28. Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells. However, cells with serious DNA damage failed to undergo cytokinesis, leading to the accumulation of multinucleated cells. Conclusion Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation. Downregulation of p21 by siRNA resulted in G2-arrested cells entering into mitosis with serious DNA damage. This is the first report on elucidating the role of p21 in the bypass of mitosis.
资助项目	National Natural Science Foundation of China[U1232125] ; National Natural Science Foundation of China[31270895] ; International Science & Technology Cooperation Program of China[2015DFR30940]
WOS关键词	CELLULAR SENESCENCE ; DNA-DAMAGE ; MITOTIC COMMITMENT ; RESTRICTION POINT ; GENOTOXIC STRESS ; G(2) ARREST ; G2 PHASE ; AURORA-A ; CYCLE ; CELLS
WOS研究方向	Environmental Sciences & Ecology ; Public, Environmental & Occupational Health
语种	英语
出版者	CHINESE CENTER DISEASE CONTROL & PREVENTION
WOS记录号	WOS:000386544700003
资助机构	National Natural Science Foundation of China ; International Science & Technology Cooperation Program of China
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/43599]
专题	中国科学院近代物理研究所
通讯作者	Lei Su Wen; Wang Ju Fang
作者单位	1.Chinese Acad Sci, Inst Modern Phys, Gansu Key Lab Space Radiobiol, Lanzhou 730000, Gansu, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Ctr Dis Control & Prevent, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zhang Xu Rui,Liu Yong Ai,Sun Fang,et al. p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis[J]. BIOMEDICAL AND ENVIRONMENTAL SCIENCES,2016,29:484-493.
APA	Zhang Xu Rui,Liu Yong Ai,Sun Fang,Li He,Lei Su Wen,&Wang Ju Fang.(2016).p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis.BIOMEDICAL AND ENVIRONMENTAL SCIENCES,29,484-493.
MLA	Zhang Xu Rui,et al."p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis".BIOMEDICAL AND ENVIRONMENTAL SCIENCES 29(2016):484-493.