NUCLEIC ACIDS

• Cells in an organism produce exact replicas of themselves
• Cells have all the information on how to make complete organisms in which they are a part
• Nucleic acids


  Molecules responsible for the information on how to make complete organisms

  
• Nucleic acids discovered by Swiss physiologist Friedrich Miescher in the nuclei of white blood cells


  1869
• Nucleic acids


  Initially found in cell nuclei and are acidic in nature

  
• Nucleic acid


  A polymer in which the monomer units are nucleotides
• Types of nucleic acids


  • DNA: Deoxyribonucleic Acid
  • RNA: Ribonucleic Acid

  
• DNA


  Storage and transfer of genetic information, passed from one cell to other during cell division
• RNA


  Primary function is to synthesize the proteins
• Components of a nucleotide


  • Pentose Sugar
  • Phosphate Group (PO43-)
  • Heterocyclic Base

  
• Pentose sugar in RNA and DNA


  Ribose is present in RNA and 2-deoxyribose is present in DNA

  
• Nitrogen-containing heterocyclic bases


  • Thymine (T)
  • Cytosine (C)
  • Uracil (U)
  • Adenine (A)
  • Guanine (G)

  
• Phosphate


  Third component of a nucleotide, derived from phosphoric acid (H3PO4) and fully dissociated to give a hydrogen phosphate ion (HPO42-) under cellular pH conditions

  
• Nucleotide formation


  1. Condensation reaction occurs at two locations: between sugar and base and between sugar and phosphate

  2. Phosphate is attached to C-5' and base is attached to C-1' position of pentose

  3. Purine bases attachment is through N-9 and for pyrimidine bases is through N-1

  4. The C-1' carbon of the pentose unit is always in a β configuration and the bond connecting the sugar and base is a β-N-glycosidic linkage

  5. The phosphate group is attached to the sugar at the C-5' position through a phosphate-ester linkage

  
• Nucleic acid backbone


  Sugar-phosphate groups found in all nucleic acids

  
• Primary structure of RNA

  A nucleotide polymer in which each of the monomers contains ribose, a phosphate group, and one of the heterocyclic bases adenine, cytosine, guanine, or uracil

  
• Primary structure of DNA


  A nucleotide polymer in which each of the monomers contains deoxyribose, a phosphate group, and one of the heterocyclic bases adenine, cytosine, guanine, or thymine

  
• Primary structure of nucleic acids


  Sequence of nucleotides in DNA or RNA, due to changes in the bases, with phosphodiester bond at 3' and 5' position, 5' end has free phosphate and 3' end has a free OH group, sequence of bases read from 5' to 3'

  
• DNA double helix


  • Two polynucleotide chains coiled around each other in a helical fashion, running antiparallel (5' - 3' and 3' - 5'), bases located at the center and hydrogen bonded (A=T and G=C), base composition: %A = %T and %C = %G

  
• Complementary bases


  Pairs of bases in a nucleic acid structure that can hydrogen-bond to each other

  
• DNA sequence and complementary strand


  • 5'-A-A-G-C-T-A-G-C-T-T-A-C-T-3'
  • 3'-T-T-C-G-A-T-C-G-A-A-T-G-A-5'
• Base pairing


  One small and one large base can fit inside the DNA strands, hydrogen bonding is stronger with A-T and G-C, A-T and G-C are called complementary bases

  
• DNA replication


  Old strands act as templates for the synthesis of new strands, DNA polymerase checks the correct base pairing and catalyzes the formation of phosphodiester linkages, newly synthesized DNA has one new DNA strand and old DNA strand

  
• DNA replication mechanism


  DNA polymerase enzyme can only function in the 5'-to-3' direction, leading strand grows continuously, lagging strand grows in segments (Okazaki fragments) in the opposite direction, segments connected by DNA ligase, replication occurs at multiple sites (origin of replication), replication is bidirectional from these sites
• Chromosomes


  Large DNA molecules interact with histone proteins to fold, histone–DNA complexes, cells of different organisms have different numbers of chromosomes, chromosomes occur in matched (homologous) pairs

  
• Identical DNA and identical twins
• Protein synthesis


  Directly under the direction of DNA, can be divided into two phases: Transcription - DNA directs the synthesis of mRNA molecules, Translation - mRNA is deciphered to synthesize a protein molecule
• Types of RNA molecules


  • Heterogeneous nuclear RNA (hnRNA)
  • Messenger RNA (mRNA)
  • Small nuclear RNA
  • Ribosomal RNA (rRNA)
  • Transfer RNA (tRNA)

  
• Transcription


  A process by which DNA directs the synthesis of mRNA molecules, two-step process - (1) synthesis of hnRNA and (2) editing to yield mRNA molecule
• Gene


  A segment of a DNA base sequence responsible for the production of a specific hnRNA/mRNA molecule, most human genes are ~1000–3500 nucleotide units long

  
• Genome


  All of the genetic material (the total DNA) contained in the chromosomes of an organism, human genome is about 20,000–25,000 genes
• Steps in the transcription process


  Unwinding of DNA double helix to expose some bases (a gene), alignment of free ribonucleotides along the exposed DNA strand (template) forming new base pairs, RNA polymerase catalyzes the linkage of ribonucleotides one by one to form mRNA molecule, transcription ends when the RNA polymerase enzyme encounters a stop signal on the DNA template

  
• Post-transcription processing: Formation of mRNA


  Involves conversion of hnRNA to mRNA, splicing: excision of introns and joining of exons, alternative splicing - a process by which several different protein variants are produced from a single gene
• Transcriptome


  All of the mRNA molecules that can be generated from the genetic material in a genome, responsible for the biochemical complexity created by splice variants obtained by hnRNA
• Genetic code


  The base sequence in a mRNA determines the amino acid sequence for the protein synthesized, codon: a three-nucleotide sequence in an mRNA molecule that codes for a specific amino acid, genetic code: the assignment of the 64 mRNA codons to specific amino acids (or stop signals), 3 of the 64 codons are termination codons ("stop" signals)

  
• Characteristics of genetic code


  • The genetic code is highly degenerate: many amino acids are designated by more than one codon
• Splicing


  Excision of one or more exons from a single gene
• Heterogenous nuclear RNA (hnRNA)


  Precursor to mRNA
• Transcriptome


  All of the mRNA molecules that can be generated from the genetic material in a genome
• Transcriptome is different from a genome