USMLE Step 1 Lecture Notes 2018: Pathology

Book Preface

CENTRAL DOGMA OF MOLECULAR BIOLOGY

An organism must be able to store and preserve its genetic information, pass that information along to future generations, and express that information as it carries out all the processes of life. The major steps involved in handling genetic information are illustrated by the central dogma of molecular biology.

Genetic information is stored in the base sequence of DNA molecules.
Ultimately, during the process of gene expression, this information is used to synthesize all the proteins made by an organism.  Classically, a gene is a unit of the DNA that encodes a particular protein or RNA molecule. Although this definition is now complicated by our increased appreciation of the ways in which genes may be expressed, it is still useful as a working definition.

Gene Expression and DNA Replication Gene expression and DNA replication are compared below. Transcription, the first stage in gene expression, involves transfer of information found in a double-stranded DNA molecule to the base sequence of a single-stranded RNA molecule. If the RNA molecule is a messenger RNA, then the process known as translation converts the information in the RNA base sequence to the amino acid sequence of a protein.

When cells divide, each daughter cell must receive an accurate copy of the
genetic information. DNA replication is the process in which each chromosome is duplicated before cell division.

The concept of the cell cycle can be used to describe the timing of some of these events in a eukaryotic cell. The M phase (mitosis) is the time in which the cell divides to form 2 daughter cells. Interphase describes the time between 2 cell divisions or mitoses. Gene expression occurs throughout all stages of interphase. Interphase is subdivided as follows: • G1 phase (gap 1) is a period of cellular growth preceding DNA synthesis. Cells that have stopped cycling, such as muscle and nerve cells, are said to be in a special state called G0. • S phase (DNA synthesis) is the period of time during which DNA replication occurs. At the end of S phase, each chromosome has doubled its DNA content and is composed of 2 identical sister chromatids linked at the centromere. • G2 phase (gap 2) is a period of cellular growth after DNA synthesis but preceding mitosis. Replicated DNA is checked for any errors before cell division.

Control of the cell cycle is accomplished at checkpoints between the various phases by strategic proteins such as cyclins and cyclin-dependent kinases. These checkpoints ensure that cells will not enter the next phase of the cycle until the molecular events in the previous cell cycle phase are concluded. Reverse transcription, which produces DNA copies of an RNA, is more commonly associated with life cycles of retroviruses, which replicate and express their genome through a DNA intermediate (an integrated provirus). Reverse transcription also occurs to a limited extent in human cells, where it plays a role in amplifying certain highly repetitive sequences in the DNA (Chapter 7).
NUCLEOTIDE STRUCTURE AND NOMENCLATURE Nucleic acids (DNA and RNA) are assembled from nucleotides, which consist of 3 components: a nitrogenous base, a 5-carbon sugar (pentose), and phosphate.

Five-Carbon Sugars Nucleic acids (as well as nucleosides and nucleotides) are classified according to the pentose they contain. If the pentose is ribose, the nucleic acid is RNA (ribonucleic acid); if the pentose is deoxyribose, the nucleic acid is DNA (deoxyribonucleic acid).
Bases There are 2 types of nitrogen-containing bases commonly found in nucleotides: purines and pyrimidines.

• Purines contain 2 rings in their structure. The purines commonly found in nucleic acids are adenine (A) and guanine (G); both are found in DNA and RNA. Other purine metabolites, not usually found in nucleic acids, include xanthine, hypoxanthine, and uric acid. • Pyrimidines have only 1 ring. Cytosine (C) is present in both DNA and RNA. Thymine (T) is usually found only in DNA, whereas uracil (U) is found only in RNA.

Nucleosides and Nucleotides Nucleosides are formed by covalently linking a base to the number 1 carbon of a sugar. The numbers identifying the carbons of the sugar are labeled with “primes” in nucleosides and nucleotides to distinguish them from the carbons of the purine or pyrimidine base.

Nucleotides are formed when 1 or more phosphate groups is attached to the 5′ carbon of a nucleoside. Nucleoside di- and triphosphates are high-energy compounds because of the hydrolytic energy associated with the acid anhydride bonds.