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INTRODUCTION

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OBJECTIVES

After studying this chapter, you should be able to:

  • Understand the chemical monomeric and polymeric structure of the genetic material, deoxyribonucleic acid, or DNA, which is found within the nucleus of eukaryotic cells.

  • Explain why genomic nuclear eukaryotic DNA is double stranded and highly negatively charged.

  • Understand the outline of how the genetic information of DNA can be faithfully duplicated.

  • Understand how the genetic information of DNA is transcribed, or copied into myriad, distinct forms of ribonucleic acid (RNA).

  • Appreciate that one form of information-rich RNA, the so-called messenger RNA (mRNA), can be subsequently translated into proteins, the molecules that form the structures, shapes, and ultimately functions of individual cells, tissues, and organs.

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BIOMEDICAL IMPORTANCE

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The discovery that genetic information is coded along the length of a polymeric molecule composed of only four types of monomeric units was one of the major scientific achievements of the 20th century. This polymeric molecule, deoxyribonucleic acid (DNA), is the chemical basis of heredity and is organized into genes, the fundamental units of genetic information. The basic information pathway—that is, DNA, which directs the synthesis of RNA, which in turn both directs and regulates protein synthesis—has been elucidated. Genes do not function autonomously; rather their replication and function are controlled by various gene products, often in collaboration with components of various signal transduction pathways. Knowledge of the structure and function of nucleic acids is essential in understanding genetics and many aspects of pathophysiology as well as the genetic basis of disease.

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DNA CONTAINS THE GENETIC INFORMATION

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The demonstration that DNA contained the genetic information was first made in 1944 in a series of experiments by Avery, MacLeod, and McCarty. They showed that the genetic determination of the character (type) of the capsule of a specific pneumococcus could be transmitted to another of a different capsular type by introducing purified DNA from the former coccus into the latter. These authors referred to the agent (later shown to be DNA) accomplishing the change as “transforming factor.” Subsequently, this type of genetic manipulation has become commonplace. Similar experiments now are regularly performed utilizing a variety of eukaryotic cells, including human cells and mammalian embryos as recipients and molecularly cloned DNA as the donor of genetic information.

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DNA Contains Four Deoxynucleotides

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The chemical nature of the monomeric deoxynucleotide units of DNA—deoxyadenylate, deoxyguanylate, deoxycytidylate, and thymidylate—is described in Chapter 32. These monomeric units of DNA are held in polymeric form by 3′,5′-phosphodiester bonds constituting a single strand, as depicted in Figure 34–1. The informational content of DNA (the genetic code) resides in the sequence in which these monomers—purine and pyrimidine deoxyribonucleotides—are ordered. The polymer as depicted possesses a polarity; one end has a 5′-hydroxyl or phosphate terminal while the other has a 3′-phosphate or hydroxyl terminal. The importance of this polarity will become evident. ...

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