H. Lodish - Molecular Cell Biology (5ed, Freeman, 2003) (796244), страница 59
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One example is the human papillomaviruses(HPVs), which most commonly cause warts and other benign skin lesions. The genomes of certain HPV serotypes,however, occasionally integrate into the chromosomal DNAof infected cervical epithelial cells, initiating development ofcervical cancer. Routine Pap smears can detect cells in theearly stages of the transformation process initiated by HPVintegration, permitting effective treatment. ❚KEY CONCEPTS OF SECTION 4.7Viruses: Parasites of the Cellular Genetic SystemViruses are small parasites that can replicate only in hostcells. Viral genomes may be either DNA (DNA viruses) orRNA (RNA viruses) and either single- or double-stranded.■The capsid, which surrounds the viral genome, is composed of multiple copies of one or a small number of virusencoded proteins.
Some viruses also have an outer envelope, which is similar to the plasma membrane but containsviral transmembrane proteins.■Most animal and plant DNA viruses require host-cellnuclear enzymes to carry out transcription of the viralgenome into mRNA and production of progeny genomes.In contrast, most RNA viruses encode enzymes that cantranscribe the RNA genome into viral mRNA and producenew copies of the RNA genome.■Host-cell ribosomes, tRNAs, and translation factors areused in the synthesis of all viral proteins in infected cells.■■ Lytic viral infection entails adsorption, penetration, synthesis of viral proteins and progeny genomes (replication),assembly of progeny virions, and release of hundreds to thousands of virions, leading to death of the host cell (see Figure 4-40).
Release of enveloped viruses occurs by buddingthrough the host-cell plasma membrane (see Figure 4-41).Nonlytic infection occurs when the viral genome is integrated into the host-cell DNA and generally does not leadto cell death.■Retroviruses are enveloped animal viruses containing asingle-stranded RNA genome. After a host cell is penetrated, reverse transcriptase, a viral enzyme carried in thevirion, converts the viral RNA genome into doublestranded DNA, which integrates into chromosomal DNA(see Figure 4-43).■Unlike infection by other retroviruses, HIV infectioneventually kills host cells, causing the defects in the immune response characteristic of AIDS.■Tumor viruses, which contain oncogenes, may have anRNA genome (e.g., human T-cell lymphotrophic virus) ora DNA genome (e.g., human papillomaviruses).
In the case■143of these viruses, integration of the viral genome into a hostcell chromosome can cause transformation of the cell intoa tumor cell.PERSPECTIVES FOR THE FUTUREIn this chapter we first reviewed the basic structure of DNAand RNA and then described fundamental aspects of thetranscription of DNA by RNA polymerases. EukaryoticRNA polymerases are discussed in greater detail in Chapter11, along with additional factors required for transcriptioninitiation in eukaryotic cells and interactions with regulatorytranscription factors that control transcription initiation.Next, we discussed the genetic code and the participation oftRNA and the protein-synthesizing machine, the ribosome,in decoding the information in mRNA to allow accurate assembly of protein chains.
Mechanisms that regulate proteinsynthesis are considered further in Chapter 12. Finally, weconsidered the molecular details underlying the accuratereplication of DNA required for cell division. Chapter 21covers the mechanisms that regulate when a cell replicates itsDNA and that coordinate DNA replication with the complexprocess of mitosis that distributes the daughter DNA molecules equally to each daughter cell.These basic cellular processes form the foundation of molecular cell biology.
Our current understanding of theseprocesses is grounded in a wealth of experimental results andis not likely to change. However, the depth of our understanding will continue to increase as additional details of thestructures and interactions of the macromolecular machinesinvolved are uncovered. The determination in recent years ofthe three-dimensional structures of RNA polymerases, ribosomal subunits, and DNA replication proteins has allowedresearchers to design ever more penetrating experimental approaches for revealing how these macromolecules operate atthe molecular level.
The detailed level of understanding thatresults may allow the design of new and more effective drugsfor treating human illnesses. For example, the recent highresolution structures of ribosomes are providing insights intothe mechanism by which antibiotics inhibit bacterial proteinsynthesis without affecting the function of mammalian ribosomes. This new knowledge may allow the design of evenmore effective antibiotics.
Similarly, detailed understandingof the mechanisms regulating transcription of specific humangenes may lead to therapeutic strategies that can reduce orprevent inappropriate immune responses that lead to multiple sclerosis and arthritis, the inappropriate cell division thatis the hallmark of cancer, and other pathological processes.Much of current biological research is focused ondiscovering how molecular interactions endow cells withdecision-making capacity and their special properties.
For thisreason several of the following chapters describe currentknowledge about how such interactions regulate transcription and protein synthesis in multicellular organisms and howsuch regulation endows cells with the capacity to become144CHAPTER 4 • Basic Molecular Genetic Mechanismsspecialized and grow into complicated organs. Other chaptersdeal with how protein-protein interactions underlie the construction of specialized organelles in cells, and how they determine cell shape and movement. The rapid advances inmolecular cell biology in recent years hold promise that in thenot too distant future we will understand how the regulationof specialized cell function, shape, and mobility coupled withregulated cell replication and cell death (apoptosis) lead to thegrowth of complex organisms like trees and human beings.KEY TERMSanticodon 119codons 119complementary 104DNA polymerases 133double helix 103envelope (viral) 137exons 111genetic code 119introns 111lagging strand 133leading strand 133messenger RNA(mRNA) 119Okazaki fragments 133operon 111phosphodiester bond 103plaque assay 138polyribosomes 130primary transcript 110primer 133promoter 109reading frame 120replication fork 133reverse transcriptase 142ribosomal RNA (rRNA) 119ribosomes 119RNA polymerase 109transcription 101transfer RNA (tRNA) 119translation 101Watson-Crick base pairs 103REVIEW THE CONCEPTS1.
What are Watson-Crick base pairs? Why are theyimportant?2. TATA box–binding protein binds to the minor grooveof DNA, resulting in the bending of the DNA helix (seeFigure 4-5). What property of DNA allows the TATAbox–binding protein to recognize the DNA helix?3. Preparing plasmid (double-stranded, circular) DNA forsequencing involves annealing a complementary, short,single-stranded oligonucleotide DNA primer to one strand ofthe plasmid template. This is routinely accomplished by heating the plasmid DNA and primer to 90 C and then slowlybringing the temperature down to 25 C. Why does this protocol work?4. What difference between RNA and DNA helps to explain the greater stability of DNA? What implications doesthis have for the function of DNA?5. What are the major differences in the synthesis andstructure of prokaryotic and eukaryotic mRNAs?6.
While investigating the function of a specific growth factor receptor gene from humans, it was found that two typesof proteins are synthesized from this gene. A larger proteincontaining a membrane-spanning domain functions to recognize growth factors at the cell surface, stimulating a specific downstream signaling pathway.
In contrast, a related,smaller protein is secreted from the cell and functions to bindavailable growth factor circulating in the blood, thus inhibiting the downstream signaling pathway. Speculate onhow the cell synthesizes these disparate proteins.7. Describe the molecular events that occur at the lacoperon when E. coli cells are shifted from a glucose-containingmedium to a lactose-containing medium.8. The concentration of free phosphate affects transcription of some E. coli genes. Describe the mechanism for this.9. Contrast how selection of the translational start site occurs on bacterial, eukaryotic, and poliovirus mRNAs.10.
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