NUCLEIC ACID

• Nucleic Acid


  The Basis of Heredity
• Nucleic Acids


  • The main function is to store and express genetic information
  • It is a naturally occurring organic macromolecule necessary for all organisms, including viruses, to function
  • Nucleic acids are generally made of 3 units - phosphate, sugars, and nitrogenous bases
  • Found inside the nucleus, hold the information that will instruct cells on what proteins to produce
  • All cellular activities are mediated by nucleic acids
• Types of Nucleic Acids

  • Ribonucleic acid (RNA)
  • Deoxyribonucleic acid (DNA)

  
• Nucleotide


  The building block of a polynucleotide

  
• Components of a Nucleotide

  • Nitrogen-containing aromatic (cyclic) base
  • Five-carbon (pentose) sugar
  • Phosphate molecule

  
• Polynucleotide

  Nucleotides connected to form short sequences (oligonucleotides) or longer sequences (polynucleotides)
• DNA

  • Every cell in a particular living thing contains the exact same DNA
  • Human DNA contains 3 billion paired deoxyribonucleotide residues and carries an estimated 25,000 genes
  • DNA is a polymer that contains polynucleotides of adenine (A), cytosine (C), guanine (G), and thymine (T), attached to an alternating sugar-phosphate backbone
  • Base pairing is always between a purine and a pyrimidine (A-T, G-C)

  
• RNA

  • RNA is a single-stranded nucleic acid polymer like DNA
  • RNA has nucleotides A, C, G, and U (Uracil replaces Thymine)
  • RNA plays an important role in protein synthesis as it bears the code from DNA

  
• Types of RNA

  • Messenger RNA (mRNA)
  • Ribosomal RNA (rRNA)
  • Transfer RNA (tRNA)

  
• Denaturation


  Increase in temperature causes the dissolution of hydrogen bonds between the DNA bases, resulting in the separation of complementary strands

  
• Renaturation/Hybridization


  When the separated DNA strands are cooled, they can reassociate and form the DNA double strand

  
• UV Absorption


  DNA absorbs UV light at a wavelength of 260 nanometers, which can be used to monitor DNA quality
• Chemical Modification


  DNA can be chemically altered by enzymes, oxidation, radiation, or exposure to carcinogens
• Central Dogma of Molecular Biology

  • Flow of genetic information from DNA to RNA to protein
  • DNA is transcribed into messenger RNA (mRNA), which is then translated into protein

  
• DNA Replication


  1. DNA forms an identical copy of itself

  2. New chains grow in 5' to 3' direction in a bidirectional manner

  3. Leading strand has continuous synthesis, lagging strand has discontinuous synthesis

  4. DNA polymerase adds nucleotides to the growing DNA chain

  5. DNA helicase unwinds the double-helical structure of DNA to allow replication

  
• DNA replication

  • Synthesis of new DNA
  • The replicated DNA is identical to parent DNA
  • New chains grow in 5' to 3' direction in bidirectional manner
  • Leading strand continuous synthesis
  • Lagging strand discontinuous synthesis
• DNA polymerase

  • Adds nucleotide one by one to the growing DNA chain
  • Incorporates complementary amino acids to the template strand

  
• DNA helicase

  • Unwinds the double-helical structure of DNA allowing DNA replication to commence

  
• DNA primase

  • Generates RNA primers, which are short RNA molecules that act as templates for the initiation of DNA replication

  
• DNA ligase

  • Joins DNA fragments together by forming phosphodiester bonds between nucleotides

  
• Topoisomerase

  • Eases the unwinding of the DNA
• Okazaki fragments

  • Pieces of DNA that are transient components of lagging strand DNA synthesis at the replication fork

  
• Leading strand

  • The new DNA strand that is continuously synthesized by the DNA polymerase enzyme
  • The primer binds to the 3′ end (start) of the strand, thus initiating the synthesize of the new strand

  
• Lagging strand

  • The template strand (5′ to 3′) that is synthesized in a discontinuous manner by RNA primers
• DNA replication process


  1. Unwinding proteins

  2. Single-strand binding proteins

  3. Primase makes RNA primer

  4. DNA polymerase makes DNA

  5. RNAse removes RNA primer

  6. DNA polymerase fills in gaps

  7. DNA ligase joins gaps

  
• Why DNA replication is important
• Transcription

  • RNA molecule is synthesized from a segment of DNA that includes a gene
  • RNA nucleotides are like DNA nucleotides but have a (slightly) different backbone
  • T is replaced with U (U = Uracil)

  
• Promoter

  • The site for RNA polymerase binding, such that the promoter guides the polymerase where it should sit on the DNA in order to initiate transcription
• RNA polymerase

  • Transcribes the information in DNA into RNA molecules that have a variety of functions, including messenger RNA (mRNA; codes for proteins), and non-coding RNAs such as transfer RNA (tRNA; transports amino acids to the ribosome for protein synthesis), ribosomal RNA (rRNA; helps catalyze protein synthesis)

  
• Template strand


  • The non-coding strand contains the complementary base pairs needed to construct the mRNA strand

  
• Translation


  • The synthesis of protein from RNA that takes place on ribosome
  • The mRNA sequence is read three bases at a time from its 5' end toward its 3' end, and one amino acid is added to the growing chain from its respective transfer RNA (tRNA), until the complete protein chain is assembled
  • Translation stops when the ribosome encounters a termination codon (UAG, UAA, or UGA)

  
• Transfer RNA (tRNA)

  • Has an anticodon for the amino acid codon it carries which are complementary to each other

  
• Anticodon

  A trinucleotide sequence complementary to that of a corresponding codon in a messenger RNA (mRNA) sequence

  
• Codon

  A trinucleotide sequence of DNA or RNA that corresponds to a specific amino acid

  
• Ribosome


  • Organizes translation and catalyzes the reaction that joins amino acids to make a protein chain
• Translating the protein

  • The start codon marks the site at which translation into protein sequence begins, and the stop codon marks the site at which translation ends
  • Start codon AUG while stop codons are UAA, UAG and UGA
• Mutation


  • A change in the DNA sequence. This change can be a result of copying mistakes during DNA synthesis, exposure to mutagens or mutating chemicals, or even radiation
  • The result of mutation can cause change in the RNA sequence that later changes the amino acid sequence
• Mutation

  • Sickle cell disease where the sixth codon of the beta globin chain – GAA is altered to GTA
• Types of nucleotide substitution mutations

  • Silent mutation – change in DNA sequence in a gene that results to no effect on the resulting amino acid sequence
  • Missense mutation – alteration of DNA sequence resulting to a different amino acid that later changes the integrity of protein
  • Nonsense mutation - a single nucleotide substitution causing abrupt stop in translation process
  • Frameshift mutation – caused by either an insertion or deletion in the DNA sequence causing a shift in the way the DNA sequence is read
• Silent mutation – change in DNA sequence in a gene that results to no effect on the resulting amino acid sequence.