B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 81
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In eukaryotes, the genome containsmultiple copies of the ribosomal RNA genes, and although they are typically clustered together in a single nucleolus, they are often located on several separatechromosomes.A variety of less obvious organelles are also present inside the nucleus. Forexample, spherical structures called Cajal bodies and interchromatin granuleclusters are present in most plant and animal cells (Figure 4–57). Like the nucleolus, these organelles are composed of selected protein and RNA molecules thatbind together to create networks that are highly permeable to other protein andRNA molecules in the surrounding nucleoplasm.Structures such as these can create distinct biochemical environments byimmobilizing select groups of macromolecules, as can other networks of proteinsand RNA molecules associated with nuclear pores and with the nuclear envelope.In principle, this allows other molecules that enter these spaces to be processedwith great efficiency through complex reaction pathways.
Highly permeable,fibrous networks of this sort can thereby impart many of the kinetic advantages ofcompartmentalization (see p. 164) to reactions that take place in subregions of thenucleus (Figure 4–58A). However, unlike the membrane-bound compartments inthe cytoplasm (discussed in Chapter 12), these nuclear subcompartments—lacking a lipid bilayer membrane—can neither concentrate nor exclude specific smallmolecules.The cell has a remarkable ability to construct distinct environments to perform complex biochemical tasks efficiently. Those that we have mentioned in thenucleus facilitate various aspects of gene expression, and will be further discussedin Chapter 6. These subcompartments, including the nucleolus, appear to form1 µmFigure 4–57 Electron micrographshowing two very common fibrousnuclear subcompartments.
The largesphere here is a Cajal body. The smallerdarker sphere is an interchromatin granulecluster, also known as a speckle (seealso Figure 6–46). These “subnuclearorganelles” are from the nucleus of aXenopus oocyte.(From K.E. HandwergerMBoC6 m4.67/4.55and J.G. Gall, Trends Cell Biol. 16:19–26,2006. With permission from Elsevier.)214Chapter 4: DNA, Chromosomes, and Genomesnuclearenvelope(A)Figure 4–58 Effective compartmentalizationwithout a bilayer membrane. (A) Schematicillustration of the organization of a sphericalsubnuclear organelle (left) and of a postulatedsimilarly organized subcompartment justbeneath the nuclear envelope (right).
Inboth cases, RNAs and/or proteins (gray)associate to form highly porous, gel-likestructures that contain binding sites for otherspecific proteins and RNA molecules (coloredobjects). (B) How the tethering of a selectedset of proteins and RNA molecules to longflexible polymer chains, as in (A), can create“staging areas” that greatly speed the rates ofreactions in subcompartments of the nucleus.The reactions catalyzed will depend on theparticular macromolecules that are localizedby the tethering. The same strategy foraccelerating complex sets of reactions is alsoemployed in subcompartments elsewhere inthe cell (see also Figure 3–78).(B)only as needed, and they create a high local concentration of the many differentenzymes and RNA molecules needed for a particular process.
In an analogousway, when DNA is damaged by irradiation, the set of enzymes needed to carry outDNA repair are observed to congregatein discrete foci inside the nucleus, creatingMBoC6 m4.69/4.56“repair factories” (see Figure 5–52). And nuclei often contain hundreds of discretefoci representing factories for DNA or RNA synthesis (see Figure 6–47).It seems likely that all of these entities make use of the type of tethering illustrated in Figure 4–58B, where long flexible lengths of polypeptide chain and/orlong noncoding RNA molecules are interspersed with specific binding sites thatconcentrate the multiple proteins and other molecules that are needed to catalyzea particular process. Not surprisingly, tethers are similarly used to help to speedbiological processes in the cytoplasm, increasing specific reaction rates there (forexample, see Figure 16–18).Is there also an intranuclear framework, analogous to the cytoskeleton, onwhich chromosomes and other components of the nucleus are organized? Thenuclear matrix, or scaffold, has been defined as the insoluble material left in thenucleus after a series of biochemical extraction steps.
Many of the proteins andRNA molecules that form this insoluble material are likely to be derived from thefibrous subcompartments of the nucleus just discussed, while others may be proteins that help to form the base of chromosomal loops or to attach chromosomesto other structures in the nucleus.Mitotic Chromosomes Are Especially Highly CondensedHaving discussed the dynamic structure of interphase chromosomes, we nowturn to mitotic chromosomes. The chromosomes from nearly all eukaryotic cellsbecome readily visible by light microscopy during mitosis, when they coil up toform highly condensed structures. This condensation reduces the length of atypical interphase chromosome only about tenfold, but it produces a dramaticchange in chromosome appearance.Figure 4–59 depicts a typical mitotic chromosome at the metaphase stageof mitosis (for the stages of mitosis, see Figure 17–3).
The two DNA moleculesproduced by DNA replication during interphase of the cell-division cycle areseparately folded to produce two sister chromosomes, or sister chromatids, heldtogether at their centromeres, as mentioned earlier. These chromosomes are normally covered with a variety of molecules, including large amounts of RNA–proteinchromosomecentromerechromatidFigure 4–59 A typical mitoticchromosome at metaphase. Each sisterchromatid contains one of two identicalsister DNA molecules generated earlier inthe cell cycle by DNA replication (see alsoFigure 17–21).MBoC6 m4.70/4.57THE GLOBAL STRUCTURE OF CHROMOSOMES215Figure 4–60 A scanning electron micrograph of a region near one endof a typical mitotic chromosome.
Each knoblike projection is believed torepresent the tip of a separate looped domain. Note that the two identicalpaired chromatids (drawn in Figure 4–59) can be clearly distinguished.(From M.P. Marsden and U.K. Laemmli, Cell 17:849–858, 1979. Withpermission from Elsevier.)complexes. Once this covering has been stripped away, each chromatid can beseen in electron micrographs to be organized into loops of chromatin emanatingfrom a central scaffolding (Figure 4–60). Experiments using DNA hybridizationto detect specific DNA sequences demonstrate that the order of visible featuresalong a mitotic chromosome at least roughly reflects the order of genes along theDNA molecule. Mitotic chromosome condensation can thus be thought of as thefinal level in the hierarchy of chromosome packaging (Figure 4–61).The compaction of chromosomes during mitosis is a highly organized anddynamic process that serves at least two important purposes.
First, when condensation is complete (in metaphase), sister chromatids have been disentangled fromeach other and lie side by side. Thus, the sister chromatids can easily separatewhen the mitotic apparatus begins pulling them apart. Second, the compactionof chromosomes protects the relatively fragile DNA molecules from being brokenas they are pulled to separate daughter cells.The condensation of interphase chromosomes into mitotic chromosomesbegins in early M phase, and it is intimately connected with the progression ofthe 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, aidthis compaction. How they help to produce the two separately folded chromatidsof a mitotic chromosome will be discussed in Chapter 17, along with the detailsof the cell cycle.short region ofDNA double helixchromatid 1chromatid 20.1 µmMBoC6 m4.71/4.582 nm11 nm“beads-on-a-string”form of chromatinchromatin fiberof packednucleosomes30 nmchromatin fiberfolded into loops700 nmcentromereentiremitoticchromosome1400 nmNET RESULT: EACH DNA MOLECULE HAS BEENPACKAGED INTO A MITOTIC CHROMOSOME THATIS 10,000-FOLD SHORTER THAN ITS FULLYEXTENDED LENGTHFigure 4–61 Chromatin packing. Thismodel shows some of the many levelsof chromatin packing postulated to giverise to the highly condensed mitoticchromosome.216Chapter 4: DNA, Chromosomes, and GenomesSummaryChromosomes are generally decondensed during interphase, so that the detailsof their structure are difficult to visualize.
Notable exceptions are the specializedlampbrush chromosomes of vertebrate oocytes and the polytene chromosomes inthe giant secretory cells of insects. Studies of these two types of interphase chromosomes suggest that each long DNA molecule in a chromosome is divided into a largenumber of discrete domains organized as loops of chromatin that are compacted byfurther folding. When genes contained in a loop are expressed, the loop unfolds andallows the cell’s machinery access to the DNA.Interphase chromosomes occupy discrete territories in the cell nucleus; that is,they are not extensively intertwined. Euchromatin makes up most of interphasechromosomes and, when not being transcribed, it probably exists as tightly foldedfibers of compacted nucleosomes.
However, euchromatin is interrupted by stretchesof heterochromatin, in which the nucleosomes are subjected to additional packingthat usually renders the DNA resistant to gene expression. Heterochromatin exists inseveral forms, some of which are found in large blocks in and around centromeresand near telomeres. But heterochromatin is also present at many other positions onchromosomes, where it can serve to help regulate developmentally important genes.The interior of the nucleus is highly dynamic, with heterochromatin often positioned near the nuclear envelope and loops of chromatin moving away from theirchromosome territory when genes are very highly expressed.
This reflects the existence of nuclear subcompartments, where different sets of biochemical reactionsare facilitated by an increased concentration of selected proteins and RNAs. Thecomponents involved in forming a subcompartment can self-assemble into discreteorganelles such as nucleoli or Cajal bodies; they can also be tethered to fixed structures such as the nuclear envelope.During mitosis, gene expression shuts down and all chromosomes adopt ahighly condensed conformation in a process that begins early in M phase to package the two DNA molecules of each replicated chromosome as two separately foldedchromatids. The condensation is accompanied by histone modifications that facilitate chromatin packing, but satisfactory completion of this orderly process, whichreduces the end-to-end distance of each DNA molecule from its interphase length byan additional factor of ten, requires additional proteins.HOW GENOMES EVOLVEIn this final section of the chapter, we provide an overview of some of the waysthat genes and genomes have evolved over time to produce the vast diversity ofmodern-day life-forms on our planet.
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