Nucleic Acids

Science — James William Steven Parker

Nucleic Acids are biological polymers that store, transmit and help express genetic information. The two principal types are DNA and RNA, although they differ substantially in sugar composition, nitrogenous bases, structure, stability and biological roles. Their fundamental building blocks are nucleotides, each containing a nitrogenous base, a pentose sugar and one or more phosphate groups. Nucleotides connect through phosphodiester bonds to form polynucleotide chains with directional backbones. The sequence of bases provides information that can be copied, transmitted and interpreted by cellular machinery. Nucleic Acids therefore form a central molecular information system underlying heredity, gene expression and many regulatory processes.

DNA contains deoxyribose sugar and commonly uses adenine, thymine, cytosine and guanine as its bases. RNA contains ribose and commonly uses adenine, uracil, cytosine and guanine. The extra hydroxyl group on ribose makes RNA chemically more reactive and generally less stable under some conditions than DNA. DNA commonly forms a double helical structure in which complementary strands are held together through hydrogen bonding and base stacking interactions. Complementarity allows one strand to provide information for copying the other. RNA can form extensive internal secondary and tertiary structures because a single RNA chain can fold back on itself and pair complementary regions.

DNA replication allows genetic information to be copied before cell division. The two DNA strands separate locally and each serves as a template for synthesis of a complementary strand. DNA polymerases add nucleotides in a direction determined by the chemistry of the growing strand, while additional proteins coordinate unwinding, primer formation, proofreading and repair. Because the two template strands have opposite orientations, replication involves different mechanisms on the two sides of the replication machinery. High fidelity is essential because copying errors can introduce mutations. Cells therefore use proofreading and multiple DNA repair pathways to maintain genome integrity, although replication is not completely error free.

Gene expression uses Nucleic Acids to connect stored sequence information with cellular function. Transcription produces RNA from a DNA template. Messenger RNA can then be translated by ribosomes into Proteins, with transfer RNA and ribosomal RNA participating in the process. Not all RNA encodes proteins. Ribosomal RNA contributes directly to ribosome structure and catalysis, transfer RNA carries amino acids during translation, and numerous regulatory RNAs influence gene expression, RNA stability, chromatin state and other processes. The separation between DNA information storage and diverse RNA functions allows biological systems to regulate genetic information at multiple levels.

Nucleic Acid structure is stabilised by several types of molecular interaction. Hydrogen bonding contributes to complementary base pairing, while base stacking interactions make an important contribution to helix stability. Ionic conditions influence the behaviour of the negatively charged phosphate backbone. DNA can adopt different helical conformations depending on sequence, hydration and environmental conditions. RNA structures can include stems, loops, bulges, pseudoknots and complex three dimensional folds. Some RNA molecules act as catalysts, demonstrating that biological information molecules can also possess direct chemical activity.

Nucleic Acids can undergo mutation, recombination, chemical modification and repair. Mutations include substitutions, insertions and deletions, while larger genomic changes can involve duplication, inversion or rearrangement. DNA damage can arise spontaneously or from environmental sources such as radiation and reactive chemicals. Repair systems identify and correct many forms of damage, including mismatched bases, damaged bases and breaks in the DNA backbone. Epigenetic modifications can alter gene activity without changing the underlying nucleotide sequence. These processes influence development, inheritance, adaptation and disease.

Nucleic Acids are central to biotechnology and medicine. Polymerase chain reaction can amplify selected DNA sequences, sequencing technologies can determine nucleotide order, and molecular cloning can propagate selected genetic material. Genome editing technologies can make targeted changes to DNA under appropriate experimental conditions. Nucleic acid based diagnostic methods can detect pathogens, mutations and other molecular markers. RNA based technologies can also use synthetic or modified RNA to influence gene expression or provide cellular instructions. The practical usefulness of these methods depends on accurate sequence information, efficient delivery and careful control of specificity and biological responses.

Nucleic Acids should not be regarded simply as passive storage molecules. DNA is both an information repository and a chemically dynamic molecule subject to repair, replication and regulation, while RNA can function as messenger, adaptor, structural component, catalyst and regulator. The information in a nucleic acid sequence does not operate independently of cellular context because gene expression depends on regulatory sequences, chromatin, transcription machinery, RNA processing, translation and environmental signals. Understanding Nucleic Acids therefore requires combining molecular structure, chemical bonding, genetics, replication, transcription, translation, regulation, mutation and biotechnology.