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[Tyrosyl-DNA phosphodiesterases: potential targets for cancer treatment]

Zhu Hu, Hao-wen Wang, Lin-kun An

    Yao Xue Xue Bao = Acta Pharmaceutica Sinica
    |June 2, 2018
    PubMed

    Insights

    Tyrosyl-DNA phosphodiesterase 1 (TDP1) and TDP2 are DNA repair enzymes crucial for genome stability. Their abnormal activity drives cancer, making TDP1 and TDP2 promising therapeutic targets for novel cancer treatments.

    Area of Science:

    • Molecular Biology
    • Genetics
    • Biochemistry

    Background:

    • DNA topoisomerases generate DNA damage from various sources, necessitating repair for genome stability.
    • Tyrosyl-DNA phosphodiesterase 1 (TDP1) and TDP2 are recently identified DNA repair enzymes.
    • TDP1 and TDP2 resolve DNA damage intermediates generated by topoisomerase 1 and 2, respectively.

    Purpose of the Study:

    • To review the role of TDP1 and TDP2 in DNA repair and cancer development.
    • To discuss the therapeutic potential of targeting TDP1 and TDP2 in cancer therapy.

    Main Methods:

    • Literature review of studies on TDP1, TDP2, topoisomerases, and cancer therapeutics.
    • Analysis of the enzymatic mechanisms of TDP1 and TDP2 in DNA repair.
    • Evaluation of the link between TDP1/TDP2 dysregulation and oncogenesis.

    Main Results:

    • TDP1 and TDP2 hydrolyze specific tyrosyl-DNA phosphodiester bonds at 3' and 5' DNA ends.
    • Abnormal activation and expression of TDP1 or TDP2 are significant contributors to cancer development.
    • TDP1 and TDP2 represent viable targets for cancer treatment strategies.

    Conclusions:

    • TDP1 and TDP2 are critical enzymes in maintaining genomic integrity.
    • Targeting TDP1 and TDP2, potentially with inhibitors, offers a promising avenue for cancer therapy.
    • Further research into TDP1 and TDP2 inhibitors could lead to novel chemotherapeutic agents.

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