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. Author manuscript; available in PMC: 2009 Nov 1.
Published in final edited form as: Nat Rev Cancer. 2009 Apr 20;9(5):338–350. doi: 10.1038/nrc2607

Figure 2. Structure of Top2 bound to DNA.

Figure 2

Dong and Berger have described a structure of the breakage reunion domain of yeast Top2 bound to DNA36. As described in the text, a key feature of the structure is the large bend induced in the DNA. Another key feature is the proximity of the TOPRIM domain and the active site tyrosine. Panel A shows the overall structure of yeast Top2 bound to DNA; the DNA is shown in yellow, while the winged helix domain helices are shown in purple. Previous studies have shown that drug resistant mutants occur near both the TOPRIM domain and the active site tyrosine. Residues labeled in blue are amino acids that are altered in drug hypersensitive top2 mutants. Pro473, is distant from the tyrosine in the primary sequence, but is close to Tyr782 in this structrure. Pro473Leu is hypersensitive to the intercalator mAMSA. Gly737 and Ser740 are both in the winged helix domain; Ser740Trp is hypersensitive to etoposide, while G737 is hypersensitive to mAMSA. Panel B shows just the region around the active site Tyr, note the presence of a Mg ion complexed within the TOPRIM domain. The figure is adapted from Rogojina and Nitiss32.