CLINICAL CASES
97
Break in the DNA sealed
Quinolones
ATP
DNA gyrase cuts both
strands of one DNA
One DNA strand passed
through the other strand
Figure 10-3. DNA gyrase action and quinolone inhibition.
topoisomerase that can remove positive supercoils from eukaryotic DNA to
prevent its tangling during replication. Quinolones inhibit eukaryotic topoiso-
merase at much higher concentrations (100 to 1000 pg/mL).
Although bacterial DNA is compacted as large circular chromosomes
with a single replication origin, most eukaryotic DNA is much more highly
organized and is associated with many proteins to form chromatin that con-
tains multiple replication origins. The general structure of chromatin has been
found to be remarkably similar in the cells of all eukaryotes. The most abun-
dant proteins associated with eukaryotic DNA (somewhat more than half its
mass) are
histones,
a family of basic proteins rich in the positively charged
amino acids lysine and/or arginine, which interact with the negatively
charged phosphate groups in DNA. There are five types of histones that are
evolutionarily conserved: H1, H2A, H2B, H3, and H4. Eight histone mole-
cules (two each of H2A, H2B, H3, and H4) form an ellipsoid approximately
11 nm long and 6.5 nm in diameter. DNA coiled around the surface of this ellip-
soid is termed the nucleosome core particle and has approximately 13/4 turns
or 166 bp before it proceeds on to the next (Figure 10-4). The complex of his-
tones plus DNA resembles a bead like structure and is called a nucleosome.
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