CLINICAL CASES
99
higher level of folding. This higher order packaging is one of the most fascinating
but also most poorly understood aspects of chromatin. Chromosomes are gener-
ally decondensed during interphase. Several studies of interphase chromosomes
have suggested that each long DNA molecule in a chromosome is divided into a
large number of discrete domains that are folded differently. The regions that are
least condensed correlate well with the regions that are actively synthesizing RNA.
All chromosomes adopt a highly condensed conformation during mitosis and
reflect a coarse heterogeneity of chromosome structure. Other complex chro-
mosomal structures found in eukaryotes are in histone-depleted metaphase chro-
mosomes. These structures form radial loops around a central fibrous protein
called
scaffold.
Most of these loops are organized into condensed 300 Ă‚ filaments
but the exact nature of these formations is not known. Nonhistone proteins, whose
hundreds of varieties constitute approximately 10 percent of chromosomal pro-
teins, are thought to be involved in these processes.
C O M P R E H E N SIO N Q U E ST IO N S
[10.1] A 38-year-old woman, who works as an administrative assistant for a
large company, opened a package and found a suspicious white pow-
der. Analysis of the powder indicates that it contained traces of the bac-
terium
Bacillus anthracis.
The woman was treated with ciprofloxacin,
an effective antibiotic. Ciprofloxacin’s mechanism of action is best
described as an inhibition of which of the following?
A. Bacterial dihydrofolate reductase
B. Bacterial peptidyl transferase activity
C. Bacterial RNA polymerase
D. DNA gyrase
E. DNA polymerase III
[10.2] The Rubenstein-Taybi syndrome (RTS) is a genetic disease that is char-
acterized by distinctive facial features, broad thumbs, broad big toes,
and mental retardation. The affected gene is
CBP
(CREB-binding pro-
tein gene), which codes for a transcriptional activator. The RTS phe-
notype is best expressed by a haploinsufficiency model, in which two
functional copies of the gene are required to produce sufficient
CBP
for proper development.
CBP
has a histone acetyltransferase activity,
which does which of the following ?
A. Inhibits RNA polymerase II
B. Helps expose the promoters of genes
C. Inhibits the splicing of heterogeneous nuclear RNA (hnRNA) to
messenger RNA (mRNA)
D. Prevents the addition of a poly-A tail to mRNA
E. Activates the formation of nucleosomes
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