5.2 The chemical stability of DNA

There are two main features of DNA that make it susceptible to damage. The first is the linkage between the deoxyribose Cl’ atom and the base (Figure 3b), a bond that is highly susceptible to hydrolysis. The other feature of DNA that contributes to its chemical instability is the presence of a large number of oxygen and ni
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4.6 Summary

  1. RNA chains play fundamentally important roles within the cell, including genetic information transfer (mRNA), components of the translation machinery (rRNA in ribosomes and tRNAs) and as regulatory small RNAs.

  2. The tertiary structure of RNA is determined by interactions that maximise base pairing. Despite instability and isolation problems, the tertiary structures of several major cellular RNAs are known.

  3. Transfer RNA struct
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Aptamers

Aptamers are nucleic acid molecules that have been developed to mimic the selective and tight binding of other molecules such as antibodies. In order to identify an aptamer that is capable of binding to a target molecule, a process called Selex (systematic evolution of ligands by exponential enrichment) is utilised. The strategy relies upon a combination of a selective binding assay and amplification by PCR. A ‘library’ of short single-stranded DNA oligonucleotides is synthesised <
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Antisense regulation of gene expression

The term antisense refers to the use of a nucleic acid that is complementary to the coding (i.e. ‘sense’) base sequence of a target gene. When nucleic acids that are antisense in nature are introduced into cells, they can hybridise to the complementary ‘sense’ mRNA through normal Watson-Crick base pairing. Synthetic antisense DNA chains as short as 15–17 nucleotides in length have been used to block specific gene expression by either physically blocking translation of the tar
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4.5 The use of nucleic acids as targeting agents

We have already described how catalytic functions such as backbone cleavage found in ribozymes can be harnessed to target destruction of specific RNAs and how hybridisation techniques are used to identify nucleic acids. In this section, we will examine two other applications of nucleic acids that depend upon their ability to base-pair and to form a wide range of secondary structures, namely antisense regulation of gene expression and the use of aptamers as structure-specific reagents.


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4.4 Ribozymes

Several types of RNA have been shown to have catalytic activity directed towards strand cleavage. They were originally observed in the case of ‘self-splicing’ introns, i.e. segments of the immature non-protein-coding mRNA that remove themselves during the formation of mature RNA, as shown in Figure 20a. The term ribozyme has been coined to describe all such catalytic RNA molecules.

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4.3 Hairpin formation and micro-RNAs

A class of small RNA molecules called micro-RNAs (miRNAs) has been identified in recent years. The roles of these small RNAs are only just beginning to be understood, but many are expressed only at specific developmental stages. Indeed, the first observations of miRNAs were made in C. elegans because of their mutant developmental phenotypes. The genes that encode these miRNAs are called mir genes (pronounced ‘meer’) and have now been identified within the genomes of v
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4.2 The structure of tRNA

Transfer RNAs are small and compact molecules. Comparisons of the base sequences of many tRNAs led to the predicted four-leaf clover structure shown in Figure 18a, which follows the rule of maximising base-pairing interactions. This structure was largely confirmed by analysis with single-strand nucleases.

Two of the four main arms of the tRNA molecule are named according to their function, i.e. binding to the mRNA trinucleotide that encodes a specific amino acid (anticodon arm),
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4.1 The varied structures of RNA

RNA is a versatile cellular molecule with the ability to adopt a number of complex structural conformations. Although RNA is often thought of as a single-stranded molecule it is actually highly structured.

SAQ 19

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Summary of Section 3

  1. Watson–Crick base pairing arises due to hydrogen bonding between A and T and G and C and spatial limitations within the hydrophobic core of the helix.

  2. DNA commonly folds into the B-form helix; other forms such as Z-DNA form in vitro. A-form helices are formed primarily by duplex RNA.

  3. The twisting of DNA around its helical axis results in torsional stresses that promote the formation of high-energy alternative confo
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3.3 Other structures in DNA

We will finish our discussion of DNA structure by examining two cases of unusual structures that can arise.


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Torsional energy can be taken up by alternative DNA conformations

The energy introduced into DNA by twisting has great potential as a regulatory mechanism, since the free energy can be stored in a variety of different high-energy conformations along the chain.

SAQ 14

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Introduction

This unit helps you understand the properties of nucleotides and how they contribute to secondary and tertiary structures of nucleic acids at the molecular level. You will learn about the different composition and roles of nucleic acids in the cell, their interactions with each other and the use of ribozymes, aptamers, antisense and hybridization as tools in molecular research. The unit covers the function of DNA packaging within the cell, the interactions between the DNA double helix and the
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2.1.1 Ron revisited

In Case Report 1 you met Ron. Ron is 59 years old, has a BMI of 31 and a central obesity ratio of 0.96, indicating that he is moderately obese, with the fat concentrated in his abdomen, rather than his hips. Clearly a number of factors, some environmental, others relating to Ron's age and all interacting with Ron's genetic constitution, may help to provide an explanation. Let's look at some of these factors in a little more detail. It is clear that Ron enjoys a comfortable lifestyle with litt
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7.2 Types of active galaxy

  • All active galaxies have a compact, energetic nucleus – an AGN.

  • Seyfert galaxies are spiral galaxies with bright, point-like nuclei which vary in brightness. They show excesses at far infrared and other wavelengths, and have strong, broad emission lines.

  • Quasars resemble very distant Seyfert galaxies with very luminous nuclei. They are variable. About 10% are strong radio sources thought to be powered by jets of material
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7.1 The spectra of galaxies

  • The spectrum of a galaxy is the composite spectrum of the objects of which it is composed.

  • The optical spectrum of a normal galaxy contains contributions from stars and HII regions. An elliptical galaxy has no HII regions and has an optical spectrum that looks somewhat like a stellar spectrum but with rather fainter absorption lines. A spiral galaxy has both stars and star-forming regions, and its optical spectrum is the composite of its st
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Radio-loud AGNs

The second model (Figure 36b) is similar to the first, but now the engine is producing a pair of jets that will eventually end in a pair of lobes, as seen in radio galaxies and some quasars.

Looking at the model from the side, one expects to see narrow lines in the spectrum (but not broad lines) and two
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Introduction

There are a wide range of different interactions between ‘science and the public’. Examples range from visiting a museum, or indulging in a science-related hobby, to reading a newspaper article about a breakthrough in the technique of therapeutic cloning, to attending a protest meeting about plans to build a waste disposal unit near to a residential area. Some such interactions are largely one-way; being a member of the audience for a ‘go-hear’ lecture, visiting a museum or‘‘liste
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10 Risk assessment exercise

After reading this unit you might like to carry out a risk assessment of your office environment or a nearby office and one of the following:

  1. a display-screen user risk assessment;

  2. a laboratory-based risk assessment;

  3. a field-work risk assessment for a proposed field expedition.


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9.3 Health

The leader must be informed of any problems of mental or physical health that may affect safety during field-work. This may include, for instance, information on diabetes, asthma or epilepsy; students should also inform the leader if they require extra assistance. All work handling living organisms, soil or water may give some risk of infection, and protection in the form of gloves, masks, etc., may need to be carried. Supervisors should give advice concerning particular health hazards that m
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