Topoisomerase Topoisomers

Fig. 4. Nucleosome relaxation, and influence of histone N-terminal tails. Example of nucleosomes on 356 bp ALk= —2.9 topoisomer from the pBR DNA minicircle series [28]. (a) Mononucleosomes (Mo) were reconstituted with control (Control) or acetylated (Acetyl) histones, incubated at 37 °C in Tris buffer [T 50 mM Tris-HCl (pH 7.5), 0.1 mM EDTA, 50 mM KCl, 5 mM MgC, and 0.5 mM dithiothreitol] or phosphate buffer [P same as Tris buffer with 50 mM potassium phosphate (pH 7.5) instead of 50 mM Tris-HCl] in the absence (Topo I —) or presence (Topo I +) of topoisomerase I, and electrophoresed in a native polyacrylamide gel at room temperature. Note the splitting of nucleosome relaxation products in two bands. TE starting chromatin in TE buffer, (b) Gel slices (brackets) were cut out, and eluted DNAs were electrophoresed in a chloroquine-containing native polyacrylamide gel, together with control naked topoisomers (C1-C4). Lanes were numbered as in the (a) gel. Autoradiograms are shown, (c) Radioactivity profiles of lanes 2 and 5 in the (b) gel. Topoisomers are indicated by their ALk values. (Adapted from Fig. 2 in Ref. [28].)...

The quinolones are inhibitors of bacterial DNA gyrase (topoisomerase II) and topoisome-rase IV. These two enzymes are essential for the uncoiling of DNA. More specifically, DNA gyrase exists as an A2B2 tetramer encoded by gyrA and gyrB genes, and... 

DNAs that differ only in linking number are called topoisomers. Enzymes that underwind and/or relax DNA, the topoisomerases, catalyze changes in linking number. The two classes of topoisomerases, type I and type II, change Lk in increments of 1 or 2, respectively, per catalytic event. 

It is now clear that topoisomerases are a diverse and important group of enzymes. Although attention has until recendy been focused on their ability to interconvert DNA topoisomers, this does not necessarily constitute the primary biological function for all of them. For instance, the recombinases Int and resolvase can relax DNA but this probably represents a side reaction of their recombination activity. It is likely that other enzymes, already known for different activities, will also be shown to be topoisomerases. Conversely, enzymes currently established as topoisomerases may be found to have other catalytic activities. Thus topoisomerases represent a rather heterogeneous class of enzymes in terms of biological function, but nevertheless share the same basic chemistry of DNA breakage and reunion. 

Both the inhibition and poisoning of topoisomerases are deleterious to cells. The collision of a transcription complex or a replication fork against a topoisomer-ase-associated DNA break interrupts RNA or DNA synthesis, and can lead to real (nontopoisomerase-bound) double-strand breaks and to gene translocations, which can trigger apoptosis and/or cancer (Li and Liu 2001). 

Topoisomers With respect to DNA, closed circular DNA molecules that are identical except in their sense or degree of supercoiling. DNA topoisomers can be interchanged only by cutting one or both strands using topoisomerases. 

R.H. Lindsey, Jr., R.P. Bender, N. Osheroff, Effects of benzene metabolites on DNA cleavage mediated by human topoisomerase II alpha 1,4-hydroquinone is a topoisomer-ase n poison, Chem. Res. Toxicol. 18 (4) (2005) 761-770. 

Anti-topoisomerase 1 (originally called anti-Scl-70 for scleroderma 70), anti-nucleolar and anticentromere. Anti-topoisomerase (anti-Scl-70) recognises the nuclear enzyme DNA topoisomer-ase 1. These antibodies are detected in 20% of SSc patients and are associated with generalised skin involvement and interstitial pulmonary disease. 

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