Nucleic Acids: DNA and RNA

Nucleic Acid Monomers

• DNA contains deoxyribose, a five-carbon sugar
• RNA contains ribose, a five-carbon sugar
• Phosphate groups are negatively charged and linked 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)

DNA vs RNA

• DNA is a double helix of two nucleotide chains winding around each other
• DNA has deoxyribose sugar, lacking one oxygen atom compared to ribose
• DNA contains the bases adenine, thymine, cytosine, and guanine
• RNA consists of a single polynucleotide chain
• RNA has ribose sugar, with an extra hydroxyl group (-OH) compared to deoxyribose
• RNA contains the bases adenine, uracil, cytosine, and guanine; uracil replaces thymine

DNA Shape

• DNA takes a double-stranded helix shape, discovered in 1953 using crystallography
• The sugar-phosphate backbone consists of deoxyribose and phosphate groups
• The nitrogenous bases are A, T, C, and G
• The two strands run in opposite directions, with one having 3' and the other 5' prime end
• Hydrogen bonds hold the strands together, which is weak but stable

Nitrogen Bases

• All five nitrogenous 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 in DNA, A-U in RNA, and C-G in both RNA and DNA
• They are essential for genetic information encoding and double helix formation

Chargaff's Rule

• Chargaff's rule states that in DNA, the amount of adenine (A) equals thymine (T), and guanine (G) equals cytosine (C)
• Adenine pairs with thymine, and guanine pairs with cytosine in the DNA structure
• Explains complementary base pairing in DNA and maintains uniform structure and diameter
• DNA replication is achieved because of the replication
• Ensures accurate copying and transmission of genetic information

DNA Replication

• DNA replication is how cells copy DNA before cell division
• Separation of strands: Parental DNA strands separate, with each serving as a template for a new strand
• Base pairing: Nucleotides pair with exposed bases on the template strands (A-T, C-G)
• Formation of new strands: DNA polymerase links nucleotides to form new strands
• Each new DNA molecule consists of one old (parental) and one new strand (semiconservative model)

Semi-Conservative Replication

• Creates two new DNA molecules, each with one original and one newly synthesized strand
• Parental DNA strands separate, each serving as a template for new strands
• Free nucleotides align along the template based on base pairing rules
• DNA polymerase links nucleotides to form the new DNA strand

Multiple Replication Origins

• Proteins attach to DNA at each origin, separating the double helix and creating replication bubbles
• Replication proceeds bidirectionally from each origin, forming new DNA strands on both sides of the bubble
• Eukaryotic chromosomes having multiple origins shortens the required time for replication
• As replication progresses, replication bubbles expand and fuse, resulting in two complete daughter DNA molecules

Replication Stages

• Initiation: Begins at replication origins, short DNA stretches with nucleotide sequences; protein initiates separation to form replication bubbles
• Elongation: DNA polymerase adds nucleotides, using the original strand as a template and adding nucleotides to the 3' end
  • The leading strand synthesizes continuously, while the other is made in Okazaki fragments joined by DNA ligase
• Termination: The replication bubble expands, combining into two complete double-stranded daughter DNA molecules

Enzymes

• DNA polymerase uses each original DNA strand as a template to build new nucleotides into its complementary strand
• RNA polymerase synthesizes the new RNA molecule, reading the DNA and assembling RNA nucleotides into a complementary RNA strand

DNA Growth Direction

• DNA elongates in the 5' to 3' direction for efficiency and accuracy

Central Dogma of Biology

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

Steps in The Central Dogma

• Transcription: A gene's DNA sequence is copied into messenger RNA (mRNA) in the nucleus of eukaryotic cells
• Eukaryotes: mRNA is processed through non-coding segments are removed and a cap and tail are added before exiting the nucleus
• Translation (RNA to Protein): mRNA goes to the cytoplasm to be translated into a polypeptide chain (protein) by ribosomes
  • Transfer RNA (tRNA) molecules bring amino acids to the ribosome, matching anticodons with mRNA codons
• Amino acid sequence in protein determines it's function and structure

Transcription

• Transfers genetic information from DNA to RNA
• RNA polymerase binds to DNA sequence for polymer initiation
• RNA polymerase adds RNA nucleotides complementary to the DNA template strands for elongation
• RNA polymerase signals the end of a gene for termination
• Nucleus for eukaryotic cells, and cytoplasm in prokaryotic

Translation

• The genetic code carried by mRNA is decoded to produce a sequence of amino acids, forming a protein
• Initiation: mRNA and ribosome subunits combine
• Elongation: Amino acids are added one by one to the polypeptide chain
• Termination: A codon signals release of the completed polypeptide, disassembling the ribosomal unit

Protein Synthesis

• Is the process in which cells build up proteins
• Transcription: Gene's DNA sequence is copied into the mRNA
• Translation: Ribosomes read the mRNA to translate it into a protein/polypeptide

Codons

• A codon is a three-nucleotide sequence in DNA or RNA that codes for a specific amino acid
• Each codon represents a single amino acid during protein synthesis

Anticodons

• An anticodon is a three-nucleotide sequence on tRNA that binds to a complementary codon on mRNA during protein synthesis
• This ensures the correct amino acid is added to the growing polypeptide chain

Amino Acids & Codons

• Most amino acids are specified by more than one codon (degeneracy) in the genetic code
  • The genetic code is redundant because many amino acids have multiple codons that code for them
  • Methionine and tryptophan are specified by only one codon each

Amino Acid Methionine

• Methionine initiates protein synthesis as the first amino acid incorporated into the polypeptide chain
• Guided by the start codon AUG on the mRNA, ensuring correct protein synthesis from the beginning

Stop Codons

• Certain codons signal the start or the end of protein translation
• The stop codons are UAA, UAG, and UGA

mRNA

• mRNA translates genetic information into proteins
• Undergoes processing to remove noncoding regions
• Binds to ribosomes to initiate translation and is regulated to ensure efficient protein synthesis

tRNA

• Translates the genetic code into proteins by carrying amino acids to the ribosome
• Matches amino acids with appropriate codons on the 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: Known as primary RNA transcripts, containing introns and exons with additional sequences (cap + tail ends)
• Post-edited mRNA: Mature mRNA where RNA splicing removes introns, exons join to form sequence, and cap + tail facilitate export/binding

Frameshift Mutations

• Occurs when nucleotides are inserted or deleted from sequence
• Alters the reading frame of the code
• Adding or subtracting nucleotides shifts the grouping of triplets
• Results in a sequence of amino acids onward leading to a nonfunctional protein
• Cause nonfunctional polypeptides and have disastrous effects on organism

Base Substitutions

• Can cause benign to severe harm depending on mutation and the location within the gene

Mutagen

• A chemical or physical agent that interacts with DNA and causes a mutation

Frederick Griffith

• Aims to develop a pneumonia vaccine by studying strains, harmless and disease-causing
• Griffith killed the bacteria then mixed dead bacteria with living bacteria
• A chemical component from the pathogenic bacteria caused a heritable change in the live harmless bacteria

Bacterial Conjugation

• Bacteria transfer DNA by contacting through the pili
• Merged membranes allow plasmids to travel back and forth, giving new information