ZHANG Xu Rui; LIU Yong Ai; SUN Fang; LI He; LEI Su Wen; WANG Ju Fang

doi:10.3967/bes2016.064

p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis

ZHANG Xu Rui, LIU Yong Ai, SUN Fang, LI He, LEI Su Wen, WANG Ju Fang

文章导航 > Biomedical and Environmental Sciences > 2016 > 29(7): 484-493

ZHANG Xu Rui, LIU Yong Ai, SUN Fang, LI He, LEI Su Wen, WANG Ju Fang. p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis[J]. Biomedical and Environmental Sciences, 2016, 29(7): 484-493. doi: 10.3967/bes2016.064

Citation:

ZHANG Xu Rui, LIU Yong Ai, SUN Fang, LI He, LEI Su Wen, WANG Ju Fang. p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis[J]. Biomedical and Environmental Sciences, 2016, 29(7): 484-493. doi: 10.3967/bes2016.064

doi: 10.3967/bes2016.064

基金项目: the National Natural Science Foundation of China [No. U1232125,31270895] and the International Science & Technology Cooperation Program of China (2015DFR30940)

p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis

Gansu Key Laboratory of Space Radiobiology, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, Gansu, China
Chinese Center for Disease Control and Prevention, Beijing 100049, China

Funds: the National Natural Science Foundation of China [No. U1232125,31270895] and the International Science & Technology Cooperation Program of China (2015DFR30940)

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-β-galactosidase (SA-β-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.
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Abstract: 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-β-galactosidase (SA-β-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.
- G2/M transition /
- DNA damage /
- Ionizing radiation /
- G2 arrest

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p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis

doi: 10.3967/bes2016.064

基金项目: the National Natural Science Foundation of China [No. U1232125,31270895] and the International Science & Technology Cooperation Program of China (2015DFR30940)

刊出日期: 2016-07-20

关键词:

G2/M transition /

DNA damage /

Ionizing radiation /

G2 arrest

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-β-galactosidase (SA-β-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.

English Abstract

p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis

Gansu Key Laboratory of Space Radiobiology, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, Gansu, China

Chinese Center for Disease Control and Prevention, Beijing 100049, China

Funds: the National Natural Science Foundation of China [No. U1232125,31270895] and the International Science & Technology Cooperation Program of China (2015DFR30940)

Publish Date: 2016-07-20

Keywords:

Abstract: 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-β-galactosidase (SA-β-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.

Citation: