Dna Is Organized Into Chromosomes

At metaphase, mammalian chromosomes possess a twofold symmetry, with the identical duplicated sister chromatids connected at a centromere, the relative po-

Figure 36-4. Illustration of the tight correlation between the presence of RNA polymerase II and RNA synthesis. A number of genes are activated when Chirono-mus tentans larvae are subjected to heat shock (39 °C for 30 minutes). A: Distribution of RNA polymerase II (also called type B) in isolated chromosome IV from the salivary gland (at arrows). The enzyme was detected by immunofluorescence using an antibody directed against the polymerase. The 5C and BR3 are specific bands of chromosome IV, and the arrows indicate puffs. B: Autoradiogram of a chromosome IV that was incubated in 3H-uridine to label the RNA. Note the correspondence of the immunofluorescence and presence of the radioactive RNA (black dots). Bar = 7 |im. (Reproduced, with permission, from Sass H: RNA polymerase B in polytene chromosomes. Cell 1982;28:274. Copyright © 1982 by the Massachusetts Institute of Technology.)

sition of which is characteristic for a given chromosome (Figure 36-5). The centromere is an adenine-thymine (A-T) rich region ranging in size from 102 (brewers' yeast) to 106 (mammals) base pairs. It binds several proteins with high affinity. This complex, called the kine-tochore, provides the anchor for the mitotic spindle. It thus is an essential structure for chromosomal segregation during mitosis.

The ends of each chromosome contain structures called telomeres. Telomeres consist of short, repeat TG-rich sequences. Human telomeres have a variable number of repeats of the sequence 5'-TTAGGG-3', which can extend for several kilobases. Telomerase, a multisubunit RNA-containing complex related to viral RNA-dependent DNA polymerases (reverse transcriptases), is the enzyme responsible for telomere synthesis and thus for maintaining the length of the telomere. Since telomere shortening has been associated with both malignant transformation and aging, telomerase has become an attractive target for cancer chemotherapy and drug development. Each sister chromatid contains one double-stranded DNA molecule. During interphase, the packing of the DNA molecule is less dense than it is in the condensed chromosome during metaphase. Metaphase chromosomes are nearly completely transcriptionally inactive.

The human haploid genome consists of about 3 X 109 bp and about 1.7 X 107 nucleosomes. Thus, each of the 23 chromatids in the human haploid genome would contain on the average 1.3 X 108 nucleotides in one double-stranded DNA molecule. The length of each DNA molecule must be compressed about 8000fold to generate the structure of a condensed metaphase chromosome! In metaphase chromosomes, the 30-nm chromatin fibers are also folded into a series of looped domains, the proximal portions of which are anchored to a nonhistone proteinaceous scaffolding within the nucleus (Figure 36-3). The packing ratios of each of the orders of DNA structure are summarized in Table 36-2.

The packaging of nucleoproteins within chromatids is not random, as evidenced by the characteristic patterns observed when chromosomes are stained with specific dyes such as quinacrine or Giemsa's stain (Figure 36-6).

From individual to individual within a single species, the pattern of staining (banding) of the entire chromosome complement is highly reproducible; nonetheless, it differs significantly from other species, even those closely related. Thus, the packaging of the nucleo-proteins in chromosomes of higher eukaryotes must in some way be dependent upon species-specific characteristics of the DNA molecules.

A combination of specialized staining techniques and high-resolution microscopy has allowed geneticists

Figure 36-5. The two sister chromatids of human chromosome 12 (x 27,850). The location of the A+T-rich centromeric region connecting sister chromatids is indicated, as are two of the four telomeres residing at the very ends of the chromatids that are attached one to the other at the centromere. (Modified and reproduced, with permission, from DuPraw EJ: DNA and Chromosomes. Holt, Rinehart, and Winston, 1970.)

to quite precisely map thousands of genes to specific regions of mouse and human chromosomes. With the recent elucidation of the human and mouse genome sequences, it has become clear that many of these visual mapping methods were remarkably accurate.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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