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Loss of ATRX sensitizes HeLa cells in response to ionizing irradiation in a manner dependent on the ATM/Chk2 pathway
Zhicheng Wang
Jilin University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7617-3165
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This work is licensed under a CC BY 4.0 License. Read Full License
Identifying novel targets for molecular radiosensitization is critical to improve the efficacy of cancer radiotherapy. Alpha-thalassemia/mental retardation X-linked (ATRX), a member of the SWI/SNF-like chromatin remodeling protein family, functions in the maintenance of genomic integrity, alternative lengthening of telomeres, and the regulation of apoptosis and senescence. However, whether ATRX is directly involved in the DNA damage response (DDR) remains unknown. Here, we show that silencing ATRX increased the sensitivity of cells to ionizing radiation (IR). IR-induced DNA damage was greater and G2/M arrest was less efficient in ATRX knockdown cells. ATRX downregulation caused defects in apoptosis and senescence, indicating that ATRX has a biological function in the DDR. ATRX loss led to failure to trigger ataxia telangiectasia-mutated (ATM) auto-phosphorylation, inhibiting the activation of ATM/Chk2 downstream effectors. These data identify ATRX as a novel target for radiosensitization, and its effect depends on inhibition of the ATM/Chk2 pathway in the DDR.
Keywords
Ionizing radiation, ATRX, ATM, DNA damage repair, cycle arrest
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This is a preprint. It has not completed peer review.
Research
Loss of ATRX sensitizes HeLa cells in response to ionizing irradiation in a manner dependent on the ATM/Chk2 pathway
Zhicheng Wang
Jilin University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7617-3165
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 21 Aug, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Identifying novel targets for molecular radiosensitization is critical to improve the efficacy of cancer radiotherapy. Alpha-thalassemia/mental retardation X-linked (ATRX), a member of the SWI/SNF-like chromatin remodeling protein family, functions in the maintenance of genomic integrity, alternative lengthening of telomeres, and the regulation of apoptosis and senescence. However, whether ATRX is directly involved in the DNA damage response (DDR) remains unknown. Here, we show that silencing ATRX increased the sensitivity of cells to ionizing radiation (IR). IR-induced DNA damage was greater and G2/M arrest was less efficient in ATRX knockdown cells. ATRX downregulation caused defects in apoptosis and senescence, indicating that ATRX has a biological function in the DDR. ATRX loss led to failure to trigger ataxia telangiectasia-mutated (ATM) auto-phosphorylation, inhibiting the activation of ATM/Chk2 downstream effectors. These data identify ATRX as a novel target for radiosensitization, and its effect depends on inhibition of the ATM/Chk2 pathway in the DDR.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6