M03.01.03 Nucleic acid

Nucleic acids are fundamental biological macromolecules responsible for storing and transmitting genetic information. They are composed of nucleotide monomers linked together in specific sequences to form long chains. This section will explore the structure, function, and key features of nucleic acids.

Structure of Nucleic Acids

Nucleotide Composition

Nucleic acids, such as DNA and RNA, are polymers made up of nucleotide units. Each nucleotide consists of three components:

• A phosphate group.
• A five-carbon sugar (deoxyribose in DNA, ribose in RNA).
• A nitrogenous base (adenine, thymine, cytosine, guanine, or uracil in RNA).

Phosphodiester Bonds

• Nucleotides are linked by 3′, 5′-phosphodiester bonds.
• A phosphate group links the 3′ carbon of one sugar to the 5′ carbon of the next sugar in the chain, resulting in a backbone structure.
• Each strand of nucleic acids has a distinct polarity with a 5′ end (often carrying a phosphate group) and a 3′ end (often carrying a hydroxyl group).

Base Sequence and Polarity

The base sequence of nucleic acids is conventionally written in the 5′ → 3′ direction (left to right). For example:

• A sequence written as 5′-TCAG-3′ can also be written as 3′-GACT-5′ if reversed.
• Phosphate positions are sometimes denoted, such as pTpCpApG.
• In DNA, “d” (deoxy) may be included: dTdCdAdG.

DNA vs. RNA

DNA Structure

• DNA (Deoxyribonucleic Acid) is generally double-stranded in eukaryotes, with the two strands running in antiparallel directions.
• Complementary base pairing occurs between adenine (A) and thymine (T) (via 2 hydrogen bonds), and between guanine (G) and cytosine (C) (via 3 hydrogen bonds).
• This complementarity ensures that the amount of A equals T and G equals C, known as Chargaff’s rules.
• DNA typically adopts a right-handed helical structure known as B-DNA, with around 10 base pairs per turn of the helix.
• A rarer form, Z-DNA, exists in G-C–-rich sequences and may be involved in gene regulation.

RNA Structure

• RNA (Ribonucleic Acid) is typically single-stranded in eukaryotes, though certain viruses may possess dsRNA genomes.
• Uracil (U) replaces thymine (T) in RNA sequences, following similar base pairing rules.

Table: Comparison of DNA and RNA

DNA Denaturation and Renaturation

Denaturation

Double-stranded DNA can be denatured by factors that disrupt hydrogen bonding and base stacking, such as:

• Heat.
• Alkaline pH.
• Chemicals like formamide and urea.

Denaturation separates DNA into two single strands, but no covalent bonds are broken.

Renaturation (Annealing)

Renatured DNA strands can form again under favorable conditions:

• When denaturing conditions are slowly removed, complementary strands rebind.
• This process is essential in techniques like Southern blotting and PCR, where a known probe DNA hybridizes with complementary target sequences.

Points to Remember

• Nucleotides are linked by 3′, 5′-phosphodiester bonds, forming the backbone of nucleic acids.
• DNA is typically double-stranded, while RNA is usually single-stranded.
• Base pairing follows Chargaff’s rules: A pairs with T, and G pairs with C in DNA.
• DNA can undergo denaturation (separation into single strands) and renaturation (reforming of the double helix).

Bibliography

1. Watson, J. D., & Crick, F. H. C. (1953). Molecular structure of nucleic acids. Nature, 171(4356), 737-738.
2. Chargaff, E. (1950). Chemical specificity of nucleic acids and mechanism of their enzymatic degradation. Experientia, 6(6), 201-209.
3. Southern, E. M. (1975). Detection of specific sequences among DNA fragments separated by gel electrophoresis. Journal of Molecular Biology, 98(3), 503-517.