Nucleic Acids

Structure of Nucleic Acids

• Nucleic acids can be broken down into smaller units called monomers, also known as nucleotides.
• A nucleotide consists of three parts: a nitrogenous base, a sugar, and a phosphoric acid residue, all covalently bonded together.
• The order of bases in the nucleic acids of DNA contains the information necessary to produce the correct amino acid sequence in the cell’s proteins.

Types of Nitrogenous Bases

• There are two types of nitrogenous bases: pyrimidines and purines.
• The pyrimidine bases are cytosine, thymine, and uracil, which are single-ring aromatic compounds.
• The purine bases are adenine and guanine, which are double-ring aromatic compounds.

Nucleosides and Nucleotides

• A nucleoside is a compound that consists of a base and a sugar covalently linked together.
• When a sugar is linked to a base, a glycosidic bond is formed between the C-1' carbon of the sugar and the N-1 nitrogen of pyrimidines or the N-9 nitrogen of purines.
• A nucleotide is formed when phosphoric acid is esterified to one of the hydroxyl groups of the sugar portion of a nucleoside.

Polymerization of Nucleotides

• The polymerization of nucleotides gives rise to nucleic acids.
• The linkage between monomers in nucleic acids involves the formation of two ester bonds by phosphoric acid.
• The resulting repeated linkage is a 3', 5'-phosphodiester bond.

Structure of DNA

• DNA consists of two polynucleotide chains wrapped around each other to form a helix.
• Hydrogen bonds between bases on opposite chains determine the alignment of the helix, with the paired bases lying in planes perpendicular to the helix axis.
• The sugar-phosphate backbone is the outer part of the helix.
• The chains run in antiparallel directions, one 3' to 5' and the other 5' to 3'.

Base Pairing

• Adenine pairs with thymine and guanine pairs with cytosine.
• A-T base pairs have two hydrogen bonds, while G-C base pairs have three hydrogen bonds.

Double Helix Structure

• The diameter of the double helix is about 20 Å (2 nm).
• The length of one complete turn of the helix along its axis is 34 Å (3.4 nm) and contains 10 base pairs.
• There are two grooves in the double helix, a large major groove and a smaller minor groove.

Variations in DNA Structure

• There are other forms of DNA, such as A-DNA, which has 11 base pairs for each turn of the helix, and Z-DNA, which is a left-handed helix.
• A-DNA is known to occur in dehydrated DNA samples and in DNA:RNA hybrids.
• Z-DNA is known to occur in nature, often with sequences of alternating purine-pyrimidine.

Supercoiling

• Supercoiling is a twisting or untwisting of the double helix, which can introduce a torsional stress.
• There are two types of supercoiling: negative supercoiling, which introduces a torsional stress that favors unwinding of the right-handed B-DNA double helix, and positive supercoiling, which overwinds such a helix.
• Enzymes called topoisomerases can change the supercoiling state of DNA.

Chromatin Structure

• Eukaryotic DNA is complexed with a number of proteins, especially with basic proteins that have abundant positively charged side chains at physiological pH.
• The resulting material is called chromatin.
• The principal proteins in chromatin are the histones, of which there are five main types.

Melting of DNA

• Heat denaturation is a way to obtain single-stranded DNA.
• The melting temperature (Tm) of DNA is dependent on the base composition, with higher percentages of G-C base pairs resulting in higher melting temperatures.

Renaturation of DNA

• Renaturation of denatured DNA is possible on slow cooling.
• The separated strands can recombine and form the same base pairs responsible for maintaining the double helix.### Replication and Transcription
• DNA replication yields two identical DNA molecules, ensuring the transmission of genetic information to daughter cells with high fidelity.
• The sequence of bases in DNA is recorded as a sequence of complementary bases in a single-stranded mRNA molecule.

Translation

• Three-base codons on the mRNA direct the sequence of amino acids in a protein.
• These codons are recognized by tRNAs carrying the appropriate amino acids.
• Ribosomes are the "machinery" for protein synthesis.

Information Transfer

• The fundamental process of information transfer in cells involves transcribing DNA into RNA, which is then translated into a protein.
• This process is encapsulated in the dogma: DNA → RNA → protein.
• The details of the process differ between prokaryotes and eukaryotes.

Types of RNA

• Transfer RNA (tRNA): transports amino acids to the site of protein synthesis.
• Ribosomal RNA (rRNA): combines with proteins to form ribosomes, the site of protein synthesis.
• Messenger RNA (mRNA): directs the amino acid sequence of proteins.
• Small nuclear RNA (snRNA): involved in the processing of initial mRNA transcripts in eukaryotes.
• Small interfering RNA (siRNA): affects gene expression; used to knock out a gene being studied.
• MicroRNA (miRNA): affects gene expression; important in growth and development.

tRNA Structure and Function

• tRNA is a single-stranded polynucleotide chain with a molecular mass of about 25,000 Da.
• Intrachain hydrogen bonding occurs in tRNA, forming A-U and G-C base pairs.
• tRNA has a cloverleaf structure, with hydrogen-bonded stems and non-hydrogen-bonded loops.
• Modified bases are present in some loops.
• tRNA folds into an L-shaped conformation to interact with the enzyme that covalently attaches an amino acid.

rRNA Structure and Function

• rRNA molecules are larger than tRNA molecules.
• rRNA combines with proteins to form ribosomes.
• Ribosomes consist of two subunits: one larger and one smaller.
• The smaller subunit consists of one large RNA molecule and about 20 different proteins.
• The larger subunit consists of two RNA molecules (in prokaryotes) or three RNA molecules (in eukaryotes) and about 35-50 different proteins.

mRNA Structure and Function

• mRNA is the least abundant of the main types of RNA.
• mRNA sequences specify the order of amino acids in proteins.
• mRNA is formed when it is needed and is degraded shortly after.
• mRNA molecules are heterogeneous in size.

snRNA Structure and Function

• snRNA is found in the nucleus of eukaryotic cells.
• snRNA is small, about 100-200 nucleotides long.
• snRNA is complexed with proteins to form small nuclear ribonucleoprotein particles (snRNPs).
• snRNPs help with the processing of initial mRNA transcripts into a mature form.

RNA Interference

• RNA interference is a process that allows for the control of gene expression.
• Short stretches of RNA (siRNAs) can be used to eliminate the expression of a specific gene.
• siRNAs are used to protect cells from viruses and to study gene expression.
• siRNA has medical applications, such as protecting liver cells from hepatitis.