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Review
. 2014 Jan;1845(1):84-9.
doi: 10.1016/j.bbcan.2013.12.002. Epub 2013 Dec 19.

Doxorubicin, DNA torsion, and chromatin dynamics

Fan Yang  1 , Sheila S Teves  1 , Christopher J Kemp  2 , Steven Henikoff  3
Affiliations
Review

Doxorubicin, DNA torsion, and chromatin dynamics

Fan Yang et al. Biochim Biophys Acta. 2014 Jan.

Abstract

Doxorubicin is one of the most important anti-cancer chemotherapeutic drugs, being widely used for the treatment of solid tumors and acute leukemias. The action of doxorubicin and other anthracycline drugs has been intensively investigated during the last several decades, but the mechanisms that have been proposed for cell killing remain disparate and controversial. In this review, we examine the proposed models for doxorubicin action from the perspective of the chromatin landscape, which is altered in many types of cancer due to recurrent mutations in chromatin modifiers. We highlight recent evidence for effects of anthracyclines on DNA torsion and chromatin dynamics that may underlie basic mechanisms of doxorubicin-mediated cell death and suggest new therapeutic strategies for cancer treatment.

Keywords: Anthracycline; Cancer; Chemotherapy; Chromatin dynamics; DNA torsion; Doxorubicin.

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Figures

Fig. 1
Fig. 1
Structure of the doxorubicin-DNA complex. (a) Doxorubicin forms a covalent bond (shown in red) with guanine on one strand of DNA mediated by formaldehyde and hydrogen bonds with guanine on the opposing strand [77]. (b) A structure of intercalation of doxorubicin into DNA. Doxorubicin intercalates into DNA and pushes apart the flanking base pairs with the sugar moiety sitting in the minor groove.
See this image and copyright information in PMC

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