An Overview of Nucleic Acid Chemistry Structure and Function

The Foundations of Molecular Biology

William B. Coleman

1. INTRODUCTION

Chemists and early biochemists determined the essential building blocks of living cells and characterized their chemical nature. Among these building blocks were nucleic acids, long-chain polymers composed of nucleotides. Nucleic acids were named based partly on their chemical properties and partly on the observation that they represent a major constituent of the cell nucleus. That nucleic acids form the chemical basis for the transmission of genetic traits was not realized until about 60 years ago (1,2). Prior to that time, there was considerable disagreement among scientists as to whether genetic information was contained in and transmitted by proteins or nucleic acids. It was recognized that chromosomes contained deoxyribonucleic acid as a primary constituent, but it was not known if this DNA carried genetic information or merely served as a scaffold for some undiscovered class of proteins that carried genetic information. However, the demonstration that genetic traits could be transmitted through DNA formed the basis for numerous investigations focused on elucidation of the nature of the genetic code. During the last halfcentury, numerous investigators have participated in the scientific revolution leading to modern molecular biology. Of particular significance were the elucidation of the structure of DNA (3-9), determination of structure-function relationships between DNA and RNA (10,11), and acquisition of basic insights into the processes of DNA replication, RNA transcription, and protein synthesis (12-19). Molecular pathology represents the application of the principles of basic molecular biology to the investigation of human disease processes. Our ever broadening insights into the molecular basis of disease processes continues to provide an opportunity for the clinical laboratory to develop and implement new and novel approaches for diagnosis and prognostic assessment of human disease.

2. THE CENTRAL DOGMA OF MOLECULAR BIOLOGY

Molecular biology has developed into a broad field of scientific pursuit and, at the same time, has come to represent a basic component of most other basic research sciences. This has come about through the rapid expansion of our insights into numerous basic aspects of molecular biology and the development of an understanding of the fundamental interaction among the several major processes that comprise the larger field of investigation. A theory, referred to as the "central dogma," describes the interrelationships among these major processes (20,21). The central dogma defines the paradigm of molecular biology that genetic information is perpetuated as sequences of nucleic acid, but that genes function by being expressed in the form of protein molecules (20). The flow of genetic information among DNA, RNA, and protein that is described by the central dogma is illustrated in Fig. 1. Individual DNA molecules serve as templates for either complementary DNA strands during the process of replication or complementary RNA molecules during the process of transcription. In turn, RNA molecules serve as blueprints for the ordering of amino acids by ribosomes during protein synthesis or translation. This simple representation of the complex interactions and interrelationships among DNA, RNA, and protein was proposed and commonly accepted shortly after the discovery of the structure of DNA. Nonetheless, this paradigm still holds more than 45 years later and continues to represent a guiding principle for molecular biologists involved in all areas of basic biological, biomedical, and genetic research.

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