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Article

Targeting bromodomain protein ANCCA/ATAD2 enhances the efficacy of DNA‑damaging chemotherapy agents and radiation

  • Authors:
    • Zhijian Duan
    • Nicolas P. Andrews
    • Christopher Z. Chen
    • Ming Fan
    • Junjian Wang
    • Jing Shen
    • Jian‑Jian Li
    • Hong‑Wu Chen
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA 95817, USA, Department of Radiation Oncology, University of California, Davis, Sacramento, CA 95817, USA, Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China
  • Pages: 318-327
    |
    Published online on: November 27, 2019
       https://doi.org/10.3892/or.2019.7418
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Abstract

Bromodomain proteins such as BRD4 chromatin regulator are attractive cancer therapeutic targets. ANCCA (AAA+ nuclear coregulatory cancer‑associated protein, also known as ATPase family AAA domain containing 2 or ATAD2) is a novel oncology drug target and contains a bromodomain and an ATPase domain. Our research group as well as others previously identified ANCCA/ATAD2 as a putative oncogene and a poor prognosis factor in many types of cancer including triple‑negative breast cancer (TNBC). In the present study, it is reported for the first time that the expression of ANCCA was highly induced by DNA‑damaging chemotherapy agents such as carboplatin, doxorubicin and mitomycin C, as well as ionizing radiation. Notably, ANCCA is required for efficient dissolution of DNA damage foci and homologous recombination. Further studies revealed that ANCCA mediates the optimal expression and activation of DNA damage response and repair factors including Chk1, Chk2 and BRCA1, and that ANCCA is recruited to the promoter of BRCA1 in response to DNA damage. Moreover, ANCCA knockdown sensitizes TNBC cells to carboplatin. Collectively, these data provide the first evidence indicating that ANCCA is a novel mediator of DNA damage response and repair and that targeting ANCCA can enhance the efficacy of radiation and chemotherapies.
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Copy and paste a formatted citation
Spandidos Publications style
Duan Z, Andrews NP, Chen CZ, Fan M, Wang J, Shen J, Li JJ and Chen HW: Targeting bromodomain protein ANCCA/ATAD2 enhances the efficacy of DNA‑damaging chemotherapy agents and radiation. Oncol Rep 43: 318-327, 2020.
APA
Duan, Z., Andrews, N.P., Chen, C.Z., Fan, M., Wang, J., Shen, J. ... Chen, H. (2020). Targeting bromodomain protein ANCCA/ATAD2 enhances the efficacy of DNA‑damaging chemotherapy agents and radiation. Oncology Reports, 43, 318-327. https://doi.org/10.3892/or.2019.7418
MLA
Duan, Z., Andrews, N. P., Chen, C. Z., Fan, M., Wang, J., Shen, J., Li, J., Chen, H."Targeting bromodomain protein ANCCA/ATAD2 enhances the efficacy of DNA‑damaging chemotherapy agents and radiation". Oncology Reports 43.1 (2020): 318-327.
Chicago
Duan, Z., Andrews, N. P., Chen, C. Z., Fan, M., Wang, J., Shen, J., Li, J., Chen, H."Targeting bromodomain protein ANCCA/ATAD2 enhances the efficacy of DNA‑damaging chemotherapy agents and radiation". Oncology Reports 43, no. 1 (2020): 318-327. https://doi.org/10.3892/or.2019.7418
Copy and paste a formatted citation
x
Spandidos Publications style
Duan Z, Andrews NP, Chen CZ, Fan M, Wang J, Shen J, Li JJ and Chen HW: Targeting bromodomain protein ANCCA/ATAD2 enhances the efficacy of DNA‑damaging chemotherapy agents and radiation. Oncol Rep 43: 318-327, 2020.
APA
Duan, Z., Andrews, N.P., Chen, C.Z., Fan, M., Wang, J., Shen, J. ... Chen, H. (2020). Targeting bromodomain protein ANCCA/ATAD2 enhances the efficacy of DNA‑damaging chemotherapy agents and radiation. Oncology Reports, 43, 318-327. https://doi.org/10.3892/or.2019.7418
MLA
Duan, Z., Andrews, N. P., Chen, C. Z., Fan, M., Wang, J., Shen, J., Li, J., Chen, H."Targeting bromodomain protein ANCCA/ATAD2 enhances the efficacy of DNA‑damaging chemotherapy agents and radiation". Oncology Reports 43.1 (2020): 318-327.
Chicago
Duan, Z., Andrews, N. P., Chen, C. Z., Fan, M., Wang, J., Shen, J., Li, J., Chen, H."Targeting bromodomain protein ANCCA/ATAD2 enhances the efficacy of DNA‑damaging chemotherapy agents and radiation". Oncology Reports 43, no. 1 (2020): 318-327. https://doi.org/10.3892/or.2019.7418
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