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Review
. 2015 Jul 22;5(3):1652-70.
doi: 10.3390/biom5031652.

Inhibition of Topoisomerase (DNA) I (TOP1): DNA Damage Repair and Anticancer Therapy

Yang Xu  1 , Chengtao Her  2
Affiliations
Review

Inhibition of Topoisomerase (DNA) I (TOP1): DNA Damage Repair and Anticancer Therapy

Yang Xu et al. Biomolecules. .

Abstract

Most chemotherapy regimens contain at least one DNA-damaging agent that preferentially affects the growth of cancer cells. This strategy takes advantage of the differences in cell proliferation between normal and cancer cells. Chemotherapeutic drugs are usually designed to target rapid-dividing cells because sustained proliferation is a common feature of cancer [1,2]. Rapid DNA replication is essential for highly proliferative cells, thus blocking of DNA replication will create numerous mutations and/or chromosome rearrangements-ultimately triggering cell death [3]. Along these lines, DNA topoisomerase inhibitors are of great interest because they help to maintain strand breaks generated by topoisomerases during replication. In this article, we discuss the characteristics of topoisomerase (DNA) I (TOP1) and its inhibitors, as well as the underlying DNA repair pathways and the use of TOP1 inhibitors in cancer therapy.

Keywords: DNA double-strand break (DSB); DNA replication; DSB repair; anticancer therapy; homologous recombination (HR); non-homologous end joining; one-ended DSB; single-strand break (SSB) repair; topoisomerase (DNA) I (TOP1); topoisomerase inhibitor.

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Figures

Figure 1
Figure 1
A schematic representation of strand passages catalyzed by three types of topoisomerases (adapted from ref. [8]).
Figure 2
Figure 2
An overview of the effects of TOP1 inhibition is provided. Inhibitors and key DNA repair factors are highlighted.
See this image and copyright information in PMC

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References

    1. Helleday T., Petermann E., Lundin C., Hodgson B., Sharma R.A. DNA repair pathways as targets for cancer therapy. Nat. Rev. Cancer. 2008;8:193–204. doi: 10.1038/nrc2342. - DOI - PubMed
    1. Hanahan D., Weinberg R.A. Hallmarks of cancer: The next generation. Cell. 2011;144:646–674. doi: 10.1016/j.cell.2011.02.013. - DOI - PubMed
    1. Branzei D., Foiani M. Maintaining genome stability at the replication fork. Nat. Rev. Mol. Cell Biol. 2010;11:208–219. doi: 10.1038/nrm2852. - DOI - PubMed
    1. Pommier Y., Leo E., Zhang H., Marchand C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol. 2010;17:421–433. doi: 10.1016/j.chembiol.2010.04.012. - DOI - PMC - PubMed
    1. Chu W.K., Hickson I.D. RecQ helicases: Multifunctional genome caretakers. Nat. Rev. Cancer. 2009;9:644–654. doi: 10.1038/nrc2682. - DOI - PubMed

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