Biology: Nucleotides and Nucleic Acids

Nucleotides: Structure and Function

• Nucleotides are essential building blocks of life, playing critical roles in DNA and RNA, energy storage and release, and cellular signaling.
• Nucleotides are composed of three main components: a nitrogen-containing base (purines or pyrimidines), a five-carbon sugar (ribose or deoxyribose), and a phosphate group.
• Purines, like adenine (A) and guanine (G), consist of a double-ring structure. Pyrimidines, like cytosine (C), thymine (T) and uracil (U), have a single-ring structure.
• Adenine (A) pairs with thymine (T) in DNA and uracil (U) in RNA, forming two hydrogen bonds. Guanine (G) pairs with cytosine (C) in both DNA and RNA, forming three hydrogen bonds.
• The sugar components in nucleotides are either ribose (in RNA) or deoxyribose (in DNA). The presence of 2'-OH group in ribose makes RNA more susceptible to alkaline hydrolysis compared to DNA.
• Nucleotides are linked through phosphodiester bonds, which form the backbone of DNA and RNA molecules.
• Sequences of nucleotides are read from the 5' end to the 3' end, with the phosphate group at the 5' end and a hydroxyl group at the 3' end.
• DNA has a higher melting temperature (Tm) than RNA due to the presence of three hydrogen bonds between G-C base pairs, compared to two hydrogen bonds between A-T base pairs.
• The stability of DNA allows it to preserve genetic information for longer periods, making it a suitable molecule for storing genetic information. RNA, despite its less stable nature, plays diverse roles in protein synthesis and other cellular processes.

DNA Structures

• There are different forms of DNA, including the standard double-stranded helix (Watson-Crick form) and alternative forms like Z-DNA, which are influenced by sequence and environmental conditions.
• Palindromic DNA sequences can form alternative structures with intra-strand base pairing, creating hairpin loops or other unique shapes.
• Some unusual DNA structures involve three or four DNA strands, like triplex DNA which forms through Hoogsteen pairing.

RNA Structures

• RNA exhibits a diverse range of secondary and tertiary structures due to its flexible backbone and ability to form non-canonical base pairs like G-U pairs.
• Transfer RNA (tRNA) plays a crucial role in translation, carrying specific amino acids to the ribosome and facilitating protein synthesis.

DNA Damage and Repair

• DNA can undergo spontaneous deamination (conversion of cytosine to uracil by a process called hydrolysis), hydrolysis of purines (adenine and guanine), and alkylation (addition of methyl groups).
• Alkylation of DNA can occur both naturally (through metabolic processes) and through exposure to chemical alkylating agents.
• Excessive methylation can cause mutations and cancer, while controlled methylation plays a role in gene regulation
• Alkylation of DNA by agents like nitrogen mustard can damage DNA and ultimately lead to cell death, making these agents useful in chemotherapy.

DNA Inhibition and Damage

• Drugs like doxorubicin inhibit DNA transcription by intercalating between GC base pairs in DNA, blocking RNA polymerase activity.
• UV radiation can damage DNA by causing photochemical reactions, leading to the formation of thymine dimers.
• Lack of UV-specific endonuclease, an enzyme that repairs thymine dimers, is responsible for the genetic disease Xeroderma pigmentosum, characterized by severe sun sensitivity.

Other Functions of Nucleotides

• They are involved in coenzyme synthesis, as in the synthesis of NAD+, NADP+, FAD and CoA.
• They are precursors of signal molecules, such as cyclic AMP, which are involved in cellular signaling pathways.