Figure 4–58 effective compartmentalization without a bilayer membrane. (A) Schematic illustration of the organization of a spherical subnuclear organelle (left) and of a postulated similarly organized subcompartment just beneath the nuclear envelope (right). In both cases, RNAs and/or proteins (gray) associate to form highly porous, gel-like structures that contain binding sites for other specific proteins and RNA molecules (colored objects). (b) How the tethering of a selected set of proteins and RNA molecules to long flexible polymer chains, as in (A), can create “staging areas” that greatly speed the rates of reactions in subcompartments of the nucleus. The reactions catalyzed will depend on the particular macromolecules that are localized by the tethering. The same strategy for accelerating complex sets of reactions is also employed in subcompartments elsewhere in the cell (see also Figure 3–78).
Figure 4–59 A typical mitotic chromosome at metaphase. Each sister chromatid contains one of two identical sister DNA molecules generated earlier in the cell cycle by DNA replication (see also Figure 17–21).
Figure 4–60 A scanning electron micrograph of a region near one end of a typical mitotic chromosome. Each knoblike projection is believed to represent the tip of a separate looped domain. Note that the two identical paired chromatids (drawn in Figure 4–59) can be clearly distinguished. (From m.P. marsden and U.k. laemmli, Cell 17:849–858, 1979. with permission from Elsevier.) complexes. Once this covering has been stripped away, each chromatid can be seen in electron micrographs to be organized into loops of chromatin emanating from a central scaffolding (Figure 4–60). Experiments using DNA hybridization to detect specific DNA sequences demonstrate that the order of visible features along a mitotic chromosome at least roughly reflects the order of genes along the DNA molecule. Mitotic chromosome condensation can thus be thought of as the final level in the hierarchy of chromosome packaging (Figure 4–61).
The compaction of chromosomes during mitosis is a highly organized and dynamic process that serves at least two important purposes. First, when condensation is complete (in metaphase), sister chromatids have been disentangled from each other and lie side by side. Thus, the sister chromatids can easily separate when the mitotic apparatus begins pulling them apart. Second, the compaction of chromosomes protects the relatively fragile DNA molecules from being broken as they are pulled to separate daughter cells.
The condensation of interphase chromosomes into mitotic chromosomes begins in early M phase, and it is intimately connected with the progression of the cell cycle. During M phase, gene expression shuts down, and specific modifications are made to histones that help to reorganize the chromatin as it compacts. Two classes of ring-shaped proteins, called cohesins and condensins, aid this compaction. How they help to produce the two separately folded chromatids of a mitotic chromosome will be discussed in Chapter 17, along with the details of the cell cycle.
short region of 11 nm form of chromatin “beads-on-a-string” chromatin fber of packed 30 nm
NET RESULT: EACH DNA MOLECULE HAS BEEN PACKAGED INTO A MITOTIC CHROMOSOME THAT IS 10,000-FOLD SHORTER THAN ITS FULLY EXTENDED LENGTH 0.1 µm
Figure 4–61 Chromatin packing. This model shows some of the many levels of chromatin packing postulated to give rise to the highly condensed mitotic chromosome.