Nucleic Acids to Proteins 1 and 2

Nucleic Acids to Proteins 1 and 2

• DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are molecules that play a fundamental role in the storage of genetic information.
• Nucleic acids are polymers that are made up of nucleotides
• Nucleotides can structurally be divided into three parts; heterocyclic base, sugar and phosphate
• The most notable difference between DNA and RNA nucleotides is the sugar; deoxyribose in DNA and ribose in RNA
• Nucleoside is a nucleotide lacking a phosphate group

• The bases in nucleosides and nucleotides are either monocyclic pyrimidines or bicyclic purines
• The pyrimidine bases are cytosine (C), thymine (T) and uracil (U)
• The purine bases are adenine (A) and guanine (G)
• Thymine is found only in DNA while uracil is found only in RNA
• Guanine and adenine are present in both DNA and RNA

• The sugars in DNA and RNA are pentoses
• They are D-ribose in RNA and 2-deoxy-D-ribose in DNA
• In all cases, the sugar is present in a five-membered acetal ring form
• The nucleobase is linked to the sugar unit through an N-glycoside bond at C1
• This linkage is always beta
• Purines are linked through N9 while pyrimidines are linked through N1
• Primed numbers are used for the sugar and non-primed numbers are used for the nucleobase atoms
• The phosphate group is nucleotides is attached via a phospho ester linkage, it may be attached to the 5' end or 3' end

• DNA is made up of long, unbranched chains of oligonucleotides which are linked via a phosphate group that joins the sugar unit with the nucleobase
• The ester linkage between nucleotides is often a phosphodiester bond
• The phosphodiester bond links a 5' of one nucleotide to the 3' of the next nucleotide
• Nucleic acids have two ends; 5' and 3'
• In some organisms, e.g. some bacteria and viruses, the 5' and 3' ends of DNA are linked to give circular DNA
• The base sequence of DNA is written from the 5' to the 3' end

• The nucleobases in DNA have the ability to form hydrogen bonds between themselves
• This property is essential to the double helix arrangement of the DNA, translation and transcription via RNA
• The polynucleotide chain of DNA coils into a helix, which gets bonded to another helical strand by hydrogen bonds between the appropriate base pairs
• In DNA the base pairs are A-T and C-G
• A-T are bonded by two hydrogen bonds while C-G are bonded by three hydrogen bonds

• The DNA double helix has two polynucleotide chains twisting on a common axis
• The bases are directed inwards to allow hydrogen bonding (base pairs)
• The sugar units and the phosphodiester bonds of the main chains form the outside part of the double helix
• The planes of the base pairs are perpendicular to the helix axis
• The helix makes a complete turn every 10 bases
• The two chains are complementary in sequence; if the identity of one chain is known the identity of the second chain can be worked out
• The chains are antiparallel

• Since the glycoside bonds between the sugars and bases of a particular base pair are not directly opposite to each other, grooved along the outside of the double helix array are unequal giving rise to what is known as the minor groove and major groove
• Grooves mainly contain water molecules, but they are distinguishable to (anticancer) small molecules

• In cell division, the DNA molecule is replicated so that each daughter cell will carry its own DNA molecule

• Interphase (DNA is copied) --> Mitosis (DNA is split equally into two daugter cell) --> Cytokinesis (Parent cell is cleaved in half)

• DNA replication proceeds in three enzymatically mediated steps: initiation, elongation and termination

• DNA replication is initiated in DNA regions known as 'origins'
• DNA replication starts by the unwinding of the DNA double strand
• This process is carried out by helicases, which break the hydrogen bonds that 'bind' the DNA strands together
• Each of the parent strands acts as a template for the synthesis of a new DNA strand
• The new DNA strands are complementary to the parent strands that act as templates
• DNA synthesis is catalysed by DNA polymerases
• Termination is achieved by blocking the replication fork and this is often achieved by DNA replication terminus site binding proteins

• The precursors for the synthesis of new DNA strands are nucleoside triphosphates
  • dCTP, dATP, DTTP, dGTP
• These triphosphate anhydrides are susceptible to nucleophilic attack from hydroxyl groups
• DNA chain extension is simply an esterification reaction of the 3'hydroxyls using the triphosphate anhydries that have the diphosphate as a good leaving group
• The correct triphosphate is selected because of the hydrogen bonding properties of the base pairs

• RNA differs structurally from DNA in three important ways
  • The sugar in RNA is ribose while in DNA it is deoxyribose
  • Thymine is replaced by uracil in RNA
  • RNA is usually single stranded
• DNA stores genetic information and RNA participate in the processes by which this information is used
• Three major forms of RNA are found in prokaryotic cells
  • mRNA
  • tRNA
  • rRNA

• It is the sequence of bases alone one DNA strand, the coding strand, which provides information for the synthesis of proteins in an organism
• A complementary second strand exists and this is termed the template strand
• A gene is a DNA segment that contains the information necessary for the synthesis of one protein
• 3 DNA bases = triplet
• 3 mRNA bases = codon

• Each amino acid in a protein is specified by a sequence of 3 nucleotides called a codon
• Every amino acid is designated 2 or 3 specific triplet codons
• The signal for starting translation is the codon of methionine, which has only one codon
• Three different codons are known as stop codons, which stop the translation process

• Although the amino acid sequence of a protein is defined by the sequence of codons in DNA, it is RNA that participates in the interpretation of this sequence
• The synthesis of mRNA from the DNA template is called transcription
• ATP, CTP, GTP and UTP are used in building the mRNA sequence
• Uracil is used instead of thymine
• The process is mediated by RNA polymerase
• Synthesis occurs in the nucleus
• First, DNA is unwinded and the template strand is the one used for the mRNA synthesis

• After synthesis, mRNA moves from the nucleus to the cytoplasm and to the ribosome
• Ribosomes are made of two subunits termed S50 and S30, which are combinations of rRNA and proteins
• A tRNA is specific for a particular amino acid
• One arm of tRNAs always has CCA to which amino acids are ligated

• The mRNA sequence is read from the 5' to the 3' in translation
• The codon and anticodon are bonded by hydrogen bonding
• In prokaryotes, the first amino acid encoded is N-formylmethionine, which has the same codon as methionine (AUG)
• The peptide is synthesis from the N-terminal to the C-termina
• The initiator aminoacyl-tRNA is bound and positioned in the P site
• The next amino acyl-tRNA is bound and positioned in the adjacent A site
• Peptide bond is formed between amino acid in A site and that in P site
• The peptide chain is now attached to the tRNA in site A
• The empty tRNA in site P is released from the ribosome
• The peptide tRNA in site A now moves to site P and a new aminoacyl tRNA moved into site A