| Xia Qi,Zhao Guoping,Wu Lijun.ZNF451 promotes DNA damage repair by recruiting 53BP1/MDC1 in A549 and HeLa cells[J].Chinese Journal of Radiological Medicine and Protection,2022,42(4):248-255 |
| ZNF451 promotes DNA damage repair by recruiting 53BP1/MDC1 in A549 and HeLa cells |
| Received:November 01, 2021 |
| DOI：10.3760/cma.j.cn112271-20211101-00435 |
| KeyWords:ZNF451|DNA damage repair|Radiosensitivity|Non-homologous end joining|53BP1/MDC1 |
| FundProject:国家自然科学基金（Y99JZ12502） |
| Author Name | Affiliation | E-mail | | Xia Qi | School of Environmental Science and Optoelectronic Technology, University of Science and Technology of China, Hefei 230026, China | | | Zhao Guoping | Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Science, Hefei 230031, China | | | Wu Lijun | School of Environmental Science and Optoelectronic Technology, University of Science and Technology of China, Hefei 230026, China | ljw@ipp.ac.cn |
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| Abstract:: |
| Objective To investigate the role of SUMO E3 ligase ZNF451 in DNA damage repair and explore the underlying mechanism in non-small cell lung cancer A549 cells and cervical cancer HeLa cells.Methods A549 cells and HeLa cells were irradiated with γ-ray irradiation or treated with etoposide. Cell proliferation viability was detected by the cell counting kit-8 assay. Protein expression was detected by Western blot assay. DNA damage repair level was detected by DR-GFP plasmid system, and the spatial positioning was detected by immunofluorescence.Results Etoposide decreased the expression level of ZNF451 in a dose- and time- dependent manner. After treatment with 30, 50, 80 μmol/L etoposide, the cell viability were reduced after the knockdown of ZNF451 in A549 and HeLa cells(A549:t=27.62, 25.61, 5.32, P<0.01; HeLa:t=30.77, 21.28, 4.18, P<0.01). Furthermore, ZNF451 was recruited at DNA damage sites. A co-localization and endogenous interaction were found between ZNF451 and γ-H2AX after the treatment of irradiation or etoposide. Moreover, the expression level of γ-H2AX was significantly increased after treatment with 30, 50, 80 μmol/L etoposide(A549:t=6.12, 10.67, 4.68, P<0.01; HeLa:t=7.94, 9.81, 15.12, P<0.01) and the repair efficiency of NHEJ was reduced in ZNF451 knockdown cells(t=18.60, P<0.05). Finally, the immunofluorescence assay showed that ZNF451 was co-localizated with 53BP1 and MDC1 after irradiation or etoposide treatment.Conclusions Knockdown of ZNF451 inhibits cell proliferation and increases the level of DNA damage in A549 and HeLa cells. ZNF451 was recruited to DNA damage sites after DSBs and participated in NHEJ repair by co-localizing with DNA damage repair factor 53BP1/MDC1. |
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