🧬Molecular Biology Unit 3 – Nucleic Acids – Structure and Function

Basic Building Blocks

• Nucleic acids consist of nucleotides which are the monomers that make up DNA and RNA
• Each nucleotide is composed of three parts: a nitrogenous base, a pentose sugar, and a phosphate group
• Nitrogenous bases in DNA include adenine (A), guanine (G), cytosine (C), and thymine (T)
  • Adenine and guanine are purines with a double-ring structure
  • Cytosine and thymine are pyrimidines with a single-ring structure
• Nitrogenous bases in RNA include adenine (A), guanine (G), cytosine (C), and uracil (U) instead of thymine
• The pentose sugar in DNA is deoxyribose, while in RNA it is ribose
  • Deoxyribose lacks a hydroxyl group at the 2' carbon compared to ribose
• Phosphate groups connect the sugars of adjacent nucleotides, forming the backbone of the nucleic acid

DNA Structure

• DNA is a double-stranded helical molecule with two antiparallel polynucleotide chains
• The two strands are held together by hydrogen bonds between complementary base pairs
  • Adenine pairs with thymine (A-T) and guanine pairs with cytosine (G-C)
  • A-T base pairs form two hydrogen bonds, while G-C base pairs form three hydrogen bonds
• The sugar-phosphate backbones are on the outside of the helix, while the nitrogenous bases are on the inside
• The double helix has a right-handed orientation and makes a complete turn every 10 base pairs
• Major and minor grooves are formed due to the asymmetric arrangement of the sugar-phosphate backbones
• The diameter of the DNA double helix is approximately 2 nm, and the distance between adjacent base pairs is 0.34 nm

RNA Structure

• RNA is typically single-stranded, but can form secondary structures through intramolecular base pairing
• The nitrogenous bases in RNA are adenine (A), guanine (G), cytosine (C), and uracil (U)
  • Uracil replaces thymine and pairs with adenine (A-U)
• RNA molecules are generally shorter than DNA molecules and have a variety of functions
  • Messenger RNA (mRNA) carries genetic information from DNA to ribosomes for protein synthesis
  • Transfer RNA (tRNA) delivers amino acids to the ribosome during translation
  • Ribosomal RNA (rRNA) is a structural and catalytic component of ribosomes
• RNA can form various secondary structures, such as hairpin loops, bulges, and internal loops
• Some RNA molecules, like ribozymes, can catalyze chemical reactions

DNA Replication

• DNA replication is the process by which a cell duplicates its genetic material before cell division
• Replication is semiconservative, meaning each newly synthesized DNA molecule contains one original strand and one new strand
• The process begins at specific sites called origins of replication
• Helicase unwinds the double helix and separates the two strands
• Single-stranded binding proteins (SSBs) stabilize the single-stranded DNA and prevent reannealing
• DNA primase synthesizes short RNA primers complementary to the single-stranded DNA
• DNA polymerase III extends the primers, synthesizing the new DNA strands in the 5' to 3' direction
  • The leading strand is synthesized continuously
  • The lagging strand is synthesized discontinuously as Okazaki fragments
• DNA polymerase I replaces the RNA primers with DNA nucleotides
• DNA ligase seals the nicks between the Okazaki fragments, creating a continuous strand

Transcription

• Transcription is the process by which genetic information in DNA is copied into RNA
• RNA polymerase recognizes and binds to promoter regions on the DNA
• The double helix is unwound, and the RNA polymerase synthesizes a complementary RNA strand from the template DNA strand
  • Uracil (U) is incorporated into the growing RNA strand instead of thymine (T)
• Transcription occurs in three stages: initiation, elongation, and termination
  • Initiation involves the assembly of the transcription complex at the promoter
  • Elongation is the process of RNA synthesis by RNA polymerase
  • Termination occurs when the RNA polymerase reaches a termination signal and releases the newly synthesized RNA
• In eukaryotes, the primary transcript (pre-mRNA) undergoes processing, including 5' capping, 3' polyadenylation, and splicing to remove introns

Translation

• Translation is the process by which the genetic information in mRNA is used to synthesize proteins
• Ribosomes, composed of rRNA and proteins, are the sites of protein synthesis
• The mRNA is read in the 5' to 3' direction, and the genetic code is read in triplets called codons
• Each codon specifies a particular amino acid or a stop signal
• tRNAs, with their attached amino acids, recognize the codons through complementary base pairing with their anticodons
• The ribosome catalyzes the formation of peptide bonds between the amino acids, creating a polypeptide chain
• Translation occurs in three stages: initiation, elongation, and termination
  • Initiation involves the assembly of the ribosomal subunits and the initiator tRNA at the start codon (AUG)
  • Elongation is the process of adding amino acids to the growing polypeptide chain
  • Termination occurs when the ribosome reaches a stop codon (UAA, UAG, or UGA) and releases the completed polypeptide

Genetic Code

• The genetic code is the set of rules that defines the relationship between codons in mRNA and amino acids in proteins
• The code is degenerate, meaning that multiple codons can specify the same amino acid
• There are 64 possible codons, 61 of which code for amino acids, and 3 are stop codons
• The code is nearly universal across all organisms, with a few exceptions in some organelles and microorganisms
• The start codon (AUG) codes for methionine and initiates translation
• Stop codons (UAA, UAG, and UGA) signal the termination of translation
• The wobble hypothesis explains the flexibility in base pairing between the third base of a codon and the first base of the tRNA anticodon

Mutations and Repair

• Mutations are changes in the DNA sequence that can alter the structure and function of proteins
• Point mutations involve the substitution, insertion, or deletion of a single nucleotide
  • Substitutions can be transitions (purine to purine or pyrimidine to pyrimidine) or transversions (purine to pyrimidine or vice versa)
  • Insertions and deletions can cause frameshift mutations if the number of bases added or removed is not a multiple of three
• Chromosomal mutations involve larger-scale changes, such as deletions, duplications, inversions, or translocations
• Mutations can be spontaneous or induced by mutagens (chemical, physical, or biological agents)
• Cells have various DNA repair mechanisms to maintain genomic integrity
  • Base excision repair removes damaged bases and replaces them with the correct nucleotides
  • Nucleotide excision repair removes bulky lesions, such as those caused by UV light
  • Mismatch repair corrects errors made during DNA replication
  • Double-strand break repair mechanisms, such as homologous recombination and non-homologous end joining, repair breaks in both strands of the DNA