DNA and RNA: Structure and Function

Nucleic Acid Monomers

• The five-carbon sugar in DNA is deoxyribose, while in RNA it is ribose.
• A phosphate group is negatively charged and links to one side of the sugar.
• Nitrogenous bases contain nitrogen and carbon.
• DNA bases: Adenine (A), Thymine (T), Cytosine (C), Guanine (G).
• RNA bases: Adenine (A), Uracil (U), Cytosine (C), Guanine (G).

Differences Between DNA and RNA

• DNA has a double helix structure, consisting of two nucleotide chains winding around each other.
• The sugar in DNA, deoxyribose, has one less oxygen atom than ribose.
• DNA bases include adenine, thymine, cytosine, and guanine.
• RNA is a single strand made of one polynucleotide chain.
• The sugar in RNA, ribose, has an extra hydroxyl group (-OH) compared to deoxyribose.
• RNA bases include adenine, uracil, cytosine, and guanine; uracil replaces thymine in RNA.

DNA Shape

• DNA has a double-stranded helix shape, discovered in 1953 using crystallography.
• The sugar-phosphate backbone consists of deoxyribose and phosphate groups.
• Nitrogenous bases in DNA are A, T, C, and G.
• The two DNA strands are complementary and run in opposite directions (3' to 5').
• Hydrogen bonds hold the strands together, which are weak but stable.

Five Nitrogen Bases

• All five nitrogen bases are part of a nucleotide.
• Pyrimidines (single ring): Thymine (DNA), Cytosine (DNA), and Uracil (RNA).
• Purines (double ring): Adenine (DNA) and Guanine (DNA).
• Base pairings: A-T (DNA), A-U (RNA), C-G (RNA and DNA).
• These bases encode genetic information and form DNA's double helix structure.

Chargaff's Rule

• States that in DNA, the amount of adenine (A) equals thymine (T), and guanine (G) equals cytosine (C).
• A pairs with T, and G pairs with C in DNA.
• Explains complementary base pairing, ensuring each base on one strand pairs with a specific base on the opposite strand.
• Maintains DNA's uniform structure and diameter.
• DNA replication is precise due to this rule.
• During cell division, DNA strands separate, and each serves as a template for a new complementary strand.
• Base pairing ensures accurate copying and transmission of genetic information.
• RNA molecules use base pairing to carry instructions from DNA for protein synthesis.

DNA Replication

• The process by which a cell copies its DNA before cell division.
• Separation of strands: Parental DNA strands separate, each serving as a template.
• Base pairing: Free nucleotides pair with exposed bases according to base pairing rules (A-T, C-G).
• Formation of new strands: Enzymes like DNA polymerase link nucleotides to form new DNA strands.
• Each new DNA molecule has one old (parental) strand and one new strand, following the semiconservative model of replication.

Semi-Conservative DNA Replication

• The mechanism by which DNA is copied in cells.
• Each new DNA molecule contains one original (parent) strand and one newly synthesized strand.
• Parental DNA strands separate.
• Each separated strand serves as a template for a new complementary strand.
• Free nucleotides align along the template based on base pairing rules.
• Enzymes, especially DNA polymerase, link nucleotides together to form a new DNA strand.

Multiple Origins of Replication

• Proteins that initiate DNA replication attach to the DNA at each origin, separating the double helix strands.
• This creates replication bubbles where DNA strands open up.
• Replication proceeds in both directions from each origin (bidirectional replication).
• Eukaryotic chromosomes have many origins of replication, shortening DNA replication time.
• Replication bubbles expand and fuse, creating two complete daughter DNA molecules.
• DNA replication is efficient and accurate.

Initiation, Elongation, and Termination

• Initiation: Starts at the origin of replication with short DNA stretches and a specific nucleotide sequence.
• Strands separate, and proteins initiate DNA replication at these origins, forming replication bubbles.
• Elongation: DNA polymerase adds new nucleotides to the strand, using the original strand as a template.
• DNA polymerase adds nucleotides only to the 3' end of the strand (5' to 3' direction).
• The leading strand is synthesized continuously, while the other is synthesized in short Okazaki fragments joined by DNA ligase.
• Termination: The replication bubble expands and combines, resulting in two complete double-stranded daughter DNA molecules.

Enzymes in DNA and RNA Synthesis

• DNA polymerase helps build new DNA, using each original DNA strand as a template to assemble new nucleotides into a complementary strand.
• RNA polymerase synthesizes new RNA molecules, reading the DNA and assembling RNA nucleotides into a complementary RNA strand.

DNA Elongation

• DNA only grows or elongates in the 5' to 3' direction due to enzyme constraints.
• This directionality is for efficiency and accuracy.

Central Dogma of Biology

• Describes the flow of genetic information: DNA → RNA → Protein.

Steps in Central Dogma

• Transcription: DNA sequence of a gene is copied into messenger RNA (mRNA) in the nucleus of eukaryotic cells.
• In eukaryotes, mRNA undergoes processing, removing non-coding segments and adding a cap and tail before leaving the nucleus.
• Translation (RNA to Protein): mRNA moves to the cytoplasm where ribosomes translate it into a polypeptide chain (protein).
• Transfer RNA (tRNA) molecules bring matching amino acids to the ribosome according to mRNA codons.
• The sequence of amino acids determines the protein's structure and function, influencing the organism's traits.

Transcription

• The process of transferring genetic information from DNA to RNA, involving a complementary RNA strand from a DNA template.
  • Initiation: RNA polymerase binds to the DNA sequence.
  • Elongation: RNA polymerase adds RNA nucleotides complementary to the DNA template strands.
  • Termination: RNA polymerase signals the end of a gene.
• Occurs in the nucleus for eukaryotic cells and in the cytoplasm for prokaryotic cells.

Translation

• The process by which the genetic code carried by mRNA is decoded to produce a specific sequence of amino acids, resulting in a polypeptide (protein).
  • Initiation: mRNA and two ribosome subunits come together.
  • Elongation: Amino acids are added one by one to the growing polypeptide chain.
  • Termination: A codon is reached, releasing the completed polypeptide and disassembling the ribosomal unit.

Protein Sythesis

• The process in which cells build proteins.
• Transcription: A gene's DNA sequence is copied in the nucleus into mRNA, which then carries genetic information from the DNA to the cytoplasm.
• Translation: Ribosomes in the cytoplasm read the mRNA and translate it into a protein chain/polypeptide.

Codons and Anticodons

• A codon is a sequence of three nucleotides in DNA or RNA that codes for a specific amino acid.
• Each codon represents a single amino acid during protein synthesis.
• An anticodon is a sequence of three nucleotides on a transfer RNA (tRNA) molecule.
• It recognizes and binds to a complementary codon on messenger RNA (mRNA) during protein synthesis.
• The anticodon ensures the correct amino acid addition to the growing polypeptide chain by matching with the specific codon on mRNA.

Amino Acids and Codons

• Most amino acids are specified by more than one codon (degeneracy in the genetic code).
  • Redundancy: The genetic code exhibits redundancy because multiple codons code for the same amino acid.
  • Exception: Methionine and tryptophan are specified by a single codon each.

Methionine

• It initiates protein synthesis.
• The first amino acid is incorporated into the polypeptide chain, guided by the start codon AUG on mRNA.

Stop Codons

• Stop codons mark the end of protein translation, including UAA, UAG, and UGA.

mRNA Function

• Translates genetic information into proteins.
• mRNA undergoes processing to remove noncoding regions, binds to ribosomes to initiate translation.
• Regulated to ensure efficient protein synthesis.

tRNA Function

• Translates the genetic code into proteins.
• Carries amino acids to the ribosome and matching them with the appropriate codons on mRNA.

Introns and Exons

• Introns: Noncoding regions within a gene that do not code for amino acids.
• Exons: Coding regions of a gene that are expressed and code for amino acids.

Pre-edited vs Post-edited mRNA

• Pre-edited mRNA: Primary RNA transcripts containing introns and exons, includes additional sequences such as a cap at the 5' end and a tail at the 3' end.
• Post-edited mRNA: Mature mRNA where introns are removed through RNA splicing, exons are joined to form a continuous coding sequence, the cap and tail are retained to facilitate export from the nucleus, protect from degradation and assist ribosome binding.

Frameshift Mutations

• Nucleotide insertions or deletions from the DNA sequence in numbers not multiples of three.
• Alters the genetic message's reading frame, shifting the grouping of triplets during translation.
• Results in a different sequence of amino acids, often leading to a nonfunctional protein.
• Causes nonfunctional polypeptides with disastrous organism effects.

Base Substitutions

• Mutations that can be benign to severe, location of mutation within the gene affects results.

Mutagen

• A chemical or physical agent that interacts with DNA and causes mutations.

Frederick Griffith Experiment

• Aimed to develop a vaccine against pneumonia by studying two strains of a bacterium (harmless and pathogenic).
• Pathogenic bacteria were killed.
• The remains of these dead bacteria were mixed with living harmless bacteria.
• A chemical component from the dead pathogenic bacteria caused a heritable change in the live harmless bacteria.

Bacterial Conjugation

• Bacteria transfer DNA from one cell to another through pili contact.
• Merged membranes let plasmids travel, each plasmid now has new information.