FUNDAMENTALS OF BIOCHEMISTRY AND MOLECULAR BIOLOGY - N. N. Skvortsova - 2016

Part I. Chemical Components of the Cell

3. NUCLEIC ACIDS

3.1. Chemical Structure AND Functions of Nitrogenous Bases, Nucleosides, NUCLEOTIDES, and Nucleic Acids

Nucleic acids play a fundamental role in the transmission of Genetic information and the Regulation of Protein Biosynthesis within the Organism.

Nucleic acids are high-molecular-weight compounds with molecular weights ranging from 20,000 to billions of daltons, whose polymer chains are constructed from monomeric units called nucleotides. Nucleotides (Fig. 30) consist of a sugar (ribose or deoxyribose), a phosphoric acid residue (phosphate), and nitrogen-containing heterocyclic bases—Purines (guanine and adenine) and Pyrimidines (cytosine, thymine, uracil):

Class="center">Fig. 30. Structural components of nucleotides

Sugars combined with a nitrogenous base form nucleosides, which are designated as adenosine, guanosine, thymidine, cytidine, and uridine, respectively (Fig. 31):

Fig. 31. Structure of nucleosides

When one, two, or three phosphate residues are attached to a nucleoside, the resulting structure is termed a nucleoside monophosphate, diphosphate, or triphosphate, respectively, or simply a nucleotide (Fig. 32):

Fig. 32. Structure of Nucleotides: adenosine mono-, di-, and triphosphate

DNA is a polymer of deoxyribonucleotides, whereas RNA is a polymer of ribonucleotides. These prefixes indicate the type of sugar moiety incorporated into the nucleic acid structure (Fig. 33):

Fig. 33. Nucleotides

The nomenclature of nucleosides serves as the basis for naming their corresponding nucleotides, while nucleosides themselves are named after the heterocyclic bases they contain. The letter designations of nucleotides within a polynucleotide chain correspond to the Abbreviations of their constituent heterocyclic bases (Table 9).

Table 9. Structural components of DNA and RNA

Differences in the Introduction/19.html">Primary Structure of DNA and RNA were discussed above. Each nucleic acid chain is built from four types of nucleotide units, and The sequence of these units within the chain can be completely arbitrary.

3.2. Complementarity of Nitrogenous Bases

The nitrogenous bases of nucleotides are capable of forming specific Base Pairs—guanine with cytosine, and adenine with thymine (in DNA) or adenine with uracil (in RNA)—during the interaction of nucleic acid chains (Fig. 34):

Fig. 34. Complementarity of nitrogenous bases

THE PRINCIPLE OF complementarity refers to the strict pairing of nitrogenous bases in DNA, where adenine binds to thymine via two Hydrogen Bonds (A = T), and guanine binds to cytosine via three hydrogen bonds (G = C).

Such interactions play a key role in A number of fundamental processes involving the storage and transmission of genetic information: METABOLISM/36.html">DNA Replication, which ensures the transmission of genetic information during Cell Division; the Transcription of DNA into RNA during protein biosynthesis; the storage of genetic information in double-stranded DNA; and DNA Repair processes upon damage.

The Nucleotide Composition of DNA obeys Erwin Chargaff's rules:

1. The amount of adenine (A) equals the amount of thymine (T), and the amount of guanine (G) equals the amount of cytosine (C):

A = T, G = C

2. The amount of purines equals the amount of pyrimidines:

A + G = T + C

The nucleotide composition of RNA does not obey such rules.

3.3. DNA: Structural Features and Organization

A DNA molecule consists of two polymer chains that form a right-handed, regular double helix (with turns of virtually identical dimensions). Note the polarity in nucleic acid molecules: the molecule possesses 5'- and 3'-ends corresponding to the carbon atom numbering in the ribose molecule (Fig. 35).

Fig. 35. Cytology/cytology/92.html">SCHEMATIC STRUCTURE OF a single DNA strand (the arrow indicates the direction in which DNA strand biosynthesis occurs)

Principles of DNA molecular architecture:

1. Irregularity. There is a regular sugar-phosphate backbone. Nitrogenous bases are attached to each sugar residue, and their sequence is irregular.

2. Antiparallelism. DNA consists of two polynucleotide chains oriented in opposite directions, with the 3'-end of one lying opposite the 5'-end of the other.

3. Complementarity. Opposite each nitrogenous base of one strand lies a strictly specific nitrogenous Base of the other strand, one being a purine and the other a pyrimidine.

4. Presence of a regular Secondary structure. The Secondary structure of DNA is a double-helical molecule whose polynucleotide chains are antiparallel and held together by hydrogen bonds between complementary bases. One turn of the helix spans 3.4 nm and contains 10 base pairs.

Two complementary, antiparallel polynucleotide chains form right-handed helices sharing a common axis (Fig. 36).

Fig. 36. Schematic representation of the secondary structure of DNA

The DNA Structure model proposed in 1953 by J. Watson and F. Crick explained genetic information coding, mutational Variability, and the replication of genes, which represent segments of the DNA molecule. Strand complementarity and nucleotide sequence constitute the chemical foundation of nucleic acid functions: the storage, replication, and transmission of hereditary information, as well as protein biosynthesis.

In an average Eukaryotic Cell, the total length of genomic DNA is about 2 m, whereas its nuclear diameter is only ~10-20 µm. Today it is known that DNA packaging (Fig. 37) within The eukaryotic nucleus occurs in several stages. First, the DNA double helix (a) is wound into nucleosomes (b); then the nucleosomal filament is folded into a so-called fibril (c), a solenoid, or a zigzag thread (d), providing additional compaction. The final panel in the figure shows a chromosome (e):

Fig. 37. Spatial packaging of DNA: a through e (see text for details)

Next, the fibril is organized into large loops (consisting of 50 thousand or more base pairs), the ends of which are anchored to the nuclear protein scaffold. Thus, the DNA of a single chromosome is packaged; however, the eukaryotic genome is divided into multiple Chromosomes. For instance, the Cells of the fruit fly Drosophila have four pairs of chromosomes, whereas human cells have 46. Individual chromosomes can be visualized under a Microscope only during mitosis.

3.4. RNA: Types and Structural Features

Cellular RNAs vary in composition, function, size, and localization. All cellular organisms rely on Ribonucleic Acids (RNAs) for Protein Synthesis. There are three MAIN TYPES OF RNA: Messenger RNA (mRNA), Transfer RNA (tRNA), and ribosomal RNA (rRNA). All RNA species are unbranched single-stranded polynucleotides that adopt specific spatial Conformations. The information governing The structure of all RNA types is stored in DNA.

The best-characterized are Transfer RNAs (tRNAs), which typically contain 76 to 85 nucleotides and have a molecular weight ranging from 25,000 to 30,000 D. tRNAs account for approximately 10% of the total cellular RNA. The primary function of tRNA is to deliver Amino Acids to the site of protein synthesis, the Ribosomes. A cell contains about 30 different tRNAs. Each tRNA possesses a unique nucleotide sequence, yet all share common secondary and tertiary spatial structures.

Ribosomal RNA (rRNA) contains between 3,000 and 5,000 nucleotides, accounting for 80–85% of the total cellular RNA. Associated with ribosomal Proteins, rRNA forms ribosomes—the Organelles responsible for protein synthesis.

Messenger (matrix) RNAs vary widely in nucleotide composition and molecular weight (up to 30,000 nucleotides), making up about 5% of the total cellular RNA. The function of mRNA is to carry genetic information from the DNA in The Nucleus to the ribosomes in the Cytoplasm. mRNA serves as the template for protein biosynthesis within The Cell. A more detailed examination of the structural features and functions of nucleic acids will be presented later in Part 3, "Fundamentals of Molecular Biology."

Selection/41.html">Review Questions and Exercises

1. Write the chemical formulas of the purine bases found in nucleic acids.

2. Write the chemical formulas of the pyrimidine bases found in nucleic acids.

3. Write the chemical formulas of the CARBOHYDRATES found in nucleic acids.

4. Write the structural formula of the DNA backbone.

5. Write the structural formula of the RNA backbone.

6. Draw the formulas of the nucleosides that make up DNA.

7. Draw the formulas of the nucleosides that make up RNA.

8. Draw the formulas of the nucleotides that differ between DNA and RNA.

9. Write the formulas of the complementary bases adenine and thymine, and indicate the positions of the hydrogen bonds between them.

10. Write the formulas of the complementary bases guanine and cytosine, and indicate the positions of the hydrogen bonds between them.

11. State Chargaff's rules of complementarity.

12. Write out a DNA fragment consisting of four nucleotides.

13. What types of bonds hold the polynucleotide chains together in the double-helical DNA molecule?

14. Explain the polarity (directionality) of a nucleic acid molecule. Illustrate your answer with a diagram.

15. List the fundamental principles of DNA molecular architecture.

16. Describe the DNA structural model proposed in 1953 by J. Watson and F. Crick.

17. List the levels of DNA packing in the nucleus of a eukaryotic cell.

18. Which proteins are involved in The formation of the Tertiary Structure of the DNA molecule?

19. What types of RNA function in the cell? Specify their sizes and functions.

20. List the differences in the primary, secondary, and tertiary structures of DNA and RNA molecules.

Tasks for Independent Work

1. Write The nucleotide sequence complementary to the given one:

2. Does the given sequence belong to a DNA or RNA polynucleotide?

3. How many pyrimidine and purine bases are contained in the given and complementary sequences?

4. Draw a diagram of the complementary base pairing between the first triplets of the given and complementary sequences.