Lodish H. - Molecular Cell Biology (5ed, Freeman, 2003) (794361), страница 61
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For example, when bacteriophage infects E. coli,the viral DNA may be integrated into the host-cell chromosome rather than being replicated. The integrated viral DNA,called a prophage, is replicated as part of the cell’s DNAfrom one host-cell generation to the next. This phenomenonis referred to as lysogeny.
Under certain conditions, theprophage DNA is activated, leading to its excision from thehost-cell chromosome, entrance into the lytic cycle, and subsequent production and release of progeny virions.142CHAPTER 4 • Basic Molecular Genetic MechanismsGenomicssRNARetrovirusproteinsReversetranscriptase51FusionBuddingHost-cellchromosomal DNANucleocapsidReversetranscriptionOverview Animation: Life Cycle of a RetrovirusMEDIA CONNECTIONS4 Transcription2ProvirusTransport tonucleus andintegration3▲ FIGURE 4-43 Retroviral life cycle.
Retroviruses havea genome of two identical copies of single-stranded RNAand an outer envelope. Step 1 : After viral glycoproteins inthe envelope interact with a specific host-cell membraneprotein, the retroviral envelope fuses directly with theplasma membrane, allowing entry of the nucleocapsidinto the cytoplasm of the cell. Step 2 : Viral reversetranscriptase and other proteins copy the viral ssRNAgenome into a double-stranded DNA.
Step 3 : The viralThe genomes of a number of animal viruses also can integrate into the host-cell genome. Probably the most important are the retroviruses, which are enveloped viruses with agenome consisting of two identical strands of RNA. Theseviruses are known as retroviruses because their RNA genomeacts as a template for formation of a DNA molecule—theopposite flow of genetic information compared with themore common transcription of DNA into RNA. In the retroviral life cycle (Figure 4-43), a viral enzyme called reversetranscriptase initially copies the viral RNA genome into singlestranded DNA complementary to the virion RNA; the sameenzyme then catalyzes synthesis of a complementary DNAstrand.
(This complex reaction is detailed in Chapter 10when we consider closely related intracellular parasites calledretrotransposons.) The resulting double-stranded DNA is integrated into the chromosomal DNA of the infected cell. Finally, the integrated DNA, called a provirus, is transcribedby the cell’s own machinery into RNA, which either is translated into viral proteins or is packaged within virion coatproteins to form progeny virions that are released by budding from the host-cell membrane.
Because most retrovirusesdo not kill their host cells, infected cells can replicate, pro-Viral DNAdsDNA is transported into the nucleus and integrated into oneof many possible sites in the host-cell chromosomal DNA. Forsimplicity, only one host-cell chromosome is depicted.
Step 4 :The integrated viral DNA (provirus) is transcribed by the host-cellRNA polymerase, generating mRNAs (dark red) and genomicRNA molecules (bright red). The host-cell machinery translatesthe viral mRNAs into glycoproteins and nucleocapsid proteins.Step 5 : Progeny virions then assemble and are released bybudding as illustrated in Figure 4-41.ducing daughter cells with integrated proviral DNA. Thesedaughter cells continue to transcribe the proviral DNA andbud progeny virions.Some retroviruses contain cancer-causing genes(oncogenes), and cells infected by such retrovirusesare oncogenically transformed into tumor cells.Studies of oncogenic retroviruses (mostly viruses of birds andmice) have revealed a great deal about the processes thatlead to transformation of a normal cell into a cancer cell(Chapter 23).Among the known human retroviruses are human T-celllymphotrophic virus (HTLV), which causes a form ofleukemia, and human immunodeficiency virus (HIV), whichcauses acquired immune deficiency syndrome (AIDS).
Bothof these viruses can infect only specific cell types, primarilycertain cells of the immune system and, in the case of HIV,some central nervous system neurons and glial cells. Onlythese cells have cell-surface receptors that interact with viralenvelope proteins, accounting for the host-cell specificity ofthese viruses. Unlike most other retroviruses, HIV eventuallykills its host cells.
The eventual death of large numbers ofPerspectives for the Futureimmune-system cells results in the defective immune response characteristic of AIDS.Some DNA viruses also can integrate into a host-cellchromosome. 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.
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