Nucleic Acids: DNA and RNA

Nucleic Acids

• Nucleic acids consist of unbranched polymers with repeating monomeric units called nucleotides.
• DNA (deoxyribonucleic acid) stores an organism's genetic information and transmits it across generations.
• RNA (ribonucleic acid) translates the genetic information in DNA into proteins for all cellular functions.
• Nucleic acids were first isolated in 1869 by Friedrich Miescher from leukocytes (pus cells).

Structural Differences Between DNA and RNA

• DNA and RNA differ in structure and function.
• DNA contains deoxyribose sugar, while RNA contains ribose sugar.
• DNA has the base thymine, while RNA has uracil.
• DNA is double-stranded; RNA is generally single-stranded.
• DNA stores RNA and protein-encoding information; RNA carries protein-encoding information, helps make proteins, and catalyzes reactions.

Nucleotides: Structural Building Blocks for Nucleic Acids

• A nucleotide is a three-subunit molecule with:
  • A pentose sugar
  • A phosphate group
  • A nitrogen-containing heterocyclic base.

Pentose Sugars

• Ribose and deoxyribose are pentose sugars that differ at the 2' carbon.

Bases

• Nucleic acid bases (nucleobases) are nitrogen-containing aromatic compounds, which make up the coding portion of nucleic acids.
• Purine bases consist of nitrogen-containing aromatic compounds, having a six-membered ring fused to a five-membered ring:
  • Adenine
  • Guanine
• Pyrimidine bases consist of nitrogen-containing aromatic compounds, having a six-membered ring:
  • Cytosine
  • Thymine
  • Uracil

Phosphate

• A phosphate group is attached to the sugar at the C5' position of the sugar through a phosphoester linkage.

Nucleotides

• Nucleotides refer to phosphoric esters of nucleosides.

Nucleotide Formation

• Pentose sugar and nitrogen-containing base react to form a two-subunit entity called a nucleoside.
• Nucleoside reacts with a phosphate group to form the three-subunit entity called a nucleotide.
• Nucleotides function as building blocks for nucleic acids.

Nucleoside Formation

• A nucleoside consists of a two-subunit molecule, with a pentose sugar bonded to a nitrogen-containing heterocyclic base.
• During nucleoside formation, the base attaches to the C1' of the sugar via a β-N-glycosidic linkage.
• Purine base attachment is through N9; pyrimidine base attachment is through N1.
• As the two molecules bond together, a water molecule forms, representing a condensation reaction.

Naming Nucleosides

• Nucleosides are named as derivatives of the base that they contain; where the base's name is modified using a suffix.
• For pyrimidine bases, the suffix -idine is used.
• Cytidine, thymidine, uridine
• For purine bases, the suffix -osine is used.
• Adenosine, guanosine
• The prefix "deoxy-" indicates the presence of deoxyribose.
• No prefix is used if the sugar is ribose.

Naming Nucleotides

• Nucleotides are named by appending '5-monophosphate' to the nucleoside name.
• The addition of a phosphate group to adenosine produces adenosine 5'-monophosphate

The Structure of DNA

• The backbone of nucleic acids consists of sugar and phosphate groups, joined together by phosphodiester bonds.

Primary Nucleic Acid Structure

• Primary nucleic acid structure defines the sequence in which nucleotides are linked together in a nucleic acid.

The Secondary Structure of DNA

• In 1953, Watson and Crick proposed a model for the secondary structure of DNA, based on:
  • DNA base composition studies by Erwin Chargaff
  • X-ray diffraction studies by Rosalind Franklin and Maurice Wilkins.

DNA's Base Composition

• Erwin Chargaff's Rules state:
  • The concentration of adenine equals that of thymine (A=T), and the concentration of guanine equals that of cytosine (G=C).
  • The ratio of G-C to A-T varies among different species.
• Only purine-pyrimidine pairs fit inside the double helix.
• Hydrogen bonds form between G-C and A-T pairs.
• Double-stranded DNA backbones run in antiparallel directions.

The DNA Double Helix

• DNA has two polynucleotide strands winding into a right-handed double helix.
• The nucleotides are linked to each other through 3',5'-phosphodiester linkages.
• The antiparallel nature of the DNA double helix refers to the fact that there is a 5' end and 3' end at both ends of the double helix.
• Nucleotide bases are on the inside of the helix, with the deoxyribose-phosphate backbone on the outside.
• The two strands of DNA in the double helix are complementary; If you know the order of bases in one strand, you can predict the order of bases in the other strand.
• The double helix contains a major groove and a minor groove.
  • The major groove is the larger of two empty spaces in an imaginary cylinder that encloses the DNA double helix
  • The minor groove is the smaller of two empty spaces in an imaginary cylinder that encloses the DNA double helix
• B-DNA represents the most common form of the DNA double helix.
• DNA can also be found in other forms, such as:
  • A-DNA
  • Z-DNA

Tertiary Structure of DNA

• Tertiary structure refers to overall three-dimensional shape, including the contribution of secondary structure.
• DNA supercoiling represents the majority of DNA molecules which are folded up (inside a cell) on themselves to create a supercoil,
• DNA is wrapped around a histone core, to generate the negative supercoil.

DNA Replication

• DNA replication refers to the process by which an exact copy of a DNA molecule is produced.
• DNA replication is semiconservative; it produces DNA molecules with one strand from the parent and a new, complementary strand.
• DNA replication begins at the replication fork, where the double helix of a DNA molecule unwinds.

RNA as the Intermediary between Genes and Proteins

• RNA acts as an intermediary between genes and proteins.
• The sugar in RNA is ribose.
• Uracil (U) takes the place of Thymine (T).
• RNA has a single strand.
• The 3 types of RNA molecules in humans are:
  • Ribosomal RNA (rRNA) comprises 80% of the total RNA and makes up the major component of the ribosomes
  • Messenger RNA (mRNA) comprises 5% of the total RNA and carries protein synthesis information from DNA to ribosomes.
  • Transfer RNA (tRNA) comprises 15% of the total RNA and brings specific amino acids to the site of protein synthesis.

From Genes to Proteins

• Transcription is the process by which RNA produces genetic information from the nucleus to the ribosomes.
• The short segment of DNA double helix unwinds, and ribonucleotides line up to create messenger RNA (mRNA).
• Translation is the process by which mRNA directs protein synthesis; mRNA divides into codons (ribonucleotide triplets) that are recognized by small amino acid carrying molecules of transfer RNA (tRNA).

Protein Synthesis

• Protein Synthesis consists of:
  • DNA Transcription
  • Activation of tRNA
  • Translation of mRNA During transcription:
• A DNA template is used to produce mRNA During activation of tRNA:
• tRNA carry specific amino acids according to their anticodons. During translation of mRNA:
• mRNA binds to ribosomes where translation begins.
• A start codon binds the first tRNA carrying the amino acid methionine to the mRNA.
• Further tRNAs then bind to and detach from the ribosome, which adds each amino acid to the polypeptide.
• The protein is then released from the ribosome,

Transcription: DNA to RNA

• During transcription, the enzyme RNA polymerase binds to DNA and separates its strands.
• The template strand of DNA is used to synthesize RNA.
• The informational strand is DNA not used for RNA synthesis.
• RNA polymerase binds to promoter regions, and similar signals cause transcription to stop.
• RNA may be edited before use.
  • Introns are portions that are cut out and discarded.
  • Exons are the remaining pieces spliced together to form the final mRNA.

The Genetic Code

• In 1954, George Gamow proposed that the genetic code consists of a sequence of three nucleotides (a triplet) coding for a specific amino acid.
• Each triplet is called a codon
• The genetic code is made up of 64 codons
• Codons are three-letter words.
• The code is degenerate.
  • Several codons may code for the same amino acid.
• The code is precise.
  • Each codon represents only a specific amino acid.
• Chain initiation is coded.
  • AUG = methionine
• Chain termination is coded.
  • UAA, UAG, and UGA - stop
• The code is almost universal.
  • GCA = alanine, perhaps, in all organisms

Codons and Anticodons

• The bases of an anticodon are complementary to bases of a codon