In 1953, James Watson and Francis Crick concluded that the DNA molecule appears as a three-dimensional double helix.
DNA consists of two polynucleotide strands that wind into a right-handed double helix.
Role of X-ray Crystallography
Rosalind Franklin and Maurice Wilkins used X-ray crystallography to study DNA's structure, which helped Watson and Crick with their discovery.
Characteristics of DNA Double Helix
The two strands run in opposite directions; one runs from the 5’ end to the 3’ end and the other runs from the 3’ end to the 5’ end.
The sugar-phosphate groups lie on the outside of the helix and the bases lie on the inside.
Complementary Base Pairs
There are complementary base pairs that always hydrogen bond together in a particular manner:
Purine = Pyrimidine
A = T; C = G
Hydrogen Bonding
Chromosome Structure
HISTONES: DNA helices wind around a core of protein molecules called histones.
NUCLEOSOMES: Group of histones in chains.
CHROMATIN: Chain of nucleosomes.
GENE: A sequence of nucleotides in DNA or RNA that encodes the synthesis of specific proteins.
Central Dogma of Molecular Biology
DNA → RNA → Protein
Replication: DNA makes a copy of itself.
Transcription: DNA is transcribed into RNA.
Translation: RNA is translated into protein.
Reverse transcription can occur from RNA to DNA. <br/>DNAReplicationDNATranscriptionRNATranslationProtein<br/>
Replication
REPLICATION is the process by which DNA makes a copy of itself when a cell divides.
SEMICONSERVATIVE REPLICATION: The original DNA molecule forms two new DNA molecules, each containing a strand from the parent DNA and one new strand.
Steps in Replication
First step in Replication is the unwinding of the DNA Helix.
The enzyme that causes the DNA Helix to unwind is called DNA Helicase.
The point at which the unwinding occurs is called Replication Fork.
Replication Process
Catalyzing the replication process is with the help of DNA Polymerase enzyme.
Leading Strand: Grows continuously; Sequence is 5’ to 3’ direction
Lagging Strand: Aka “Okazaki Fragments”; Synthesized in small fragments; Sequence is 3’ to 5’ direction
DNA Ligase – enzyme that joins the lagging strand together.
End Result of Replication
The end result of the Replication Process is the formation of two new strands of DNA (Daughter DNA).
RNA vs DNA
Feature
RNA
DNA
LOCATION
In all parts of the cell
Within the nucleus
STRUCTURE
Single-stranded
Double-stranded
SUGAR
Ribose
Deoxyribose
Base Pairing
A=U; G=C
A=T; G=C
FUNCTION
Synthesis of proteins
Storage and transfer of genetic information
Transcription
Is the ordered synthesis of RNA from DNA; the genetic information stored in DNA is passed onto RNA
Three types of RNA molecules:
Ribosomal RNA (rRNA)
Messenger RNA (mRNA)
Transfer RNA (tRNA)
Types of RNA
Ribosomal RNA (rRNA): Provides the site where polypeptides are assembled during protein synthesis.
Messenger RNA (mRNA): Carries information from DNA to the ribosomes.
Transfer RNA (tRNA): Brings the amino acids to the ribosomes for protein synthesis.
tRNA Structure
tRNA is drawn as a cloverleaf shape, with an acceptor stem at the 3’ end, which carries the needed amino acids, and an anticodon, which identifies the needed amino acids.
Transcription Process
Transcription is the synthesis of mRNA from the DNA.
Template strand: Used to synthesize RNA.
Informational strand: Not used; “non-template strand”
Direction of Transcription
Transcription proceeds from the 3’ end to the 5’ end of the template.
The difference between mRNA and the information DNA strand is that the base U replaces T on mRNA.
RNA Polymerase
RNA Polymerase is the enzyme that synthesizes RNA from a DNA template in the transcription process.
Sample Problems (Transcription)
Problems demonstrating how to derive the mRNA and informational strand from a template DNA strand.
Given the template strand 3’ – C T A G G A T A C – 5’, the mRNA strand is 5’ – G A U C C U A U G – 3’ and the informational strand is 5’ – G A T C C T A T G – 3’.
Given the template strand 3’ – G C T T C G T G G C – 5’, the mRNA strand is 5’ – C G A A G C A C C G – 3’ and the informational strand is 5’ – C G A A G C A C C G – 3’.
The Genetic Code
A sequence of three nucleotides (a triplet) codes for a specific amino acid.
Each triplet is called a codon.
For example: UCA is a codon for the amino acid Serine; UGC is a codon for the amino acid Cysteine.
Translation and Protein Synthesis
Process of transferring genetic information from RNA to a sequence of amino acids in a protein.
Occurs in ribosomes.
mRNA Codon and tRNA Anticodon
The mRNA codon is matched by the tRNA anticodon to bring the correct amino acid.
Examples: ACA, GCG, AGA, UCC (mRNA codons).
Three Stages of Translation
1. INITIATION
Initiation begins with mRNA binding to ribosome.
A tRNA brings the first amino acid, always at codon AUG.
AUG = START CODON
AUG = Methionine
2. ELONGATION
Elongation proceeds as the next tRNA molecule delivers the next amino acid, and a peptide bond forms between the two amino acids.
3. TERMINATION
Translation continues until a stop codon is reached, which is called termination; the completed protein is then released.
STOP CODONS: UAG, UGA, UAA
Translation Examples
Examples showing the relationship between DNA template strand, mRNA, tRNA anticodons, and the resulting polypeptide.
DNA template strand: TAC AAC CCT CGG CCT AGT
DNA template strand: TAC GGC CGC AAG CAT TGT
Mutations and Genetic Diseases
A mutation is a change in the nucleotide sequence in a molecule of DNA.
Some mutations are random, others are caused by mutagens – chemicals that alter the structure of DNA.
Point Mutations
A point mutation is the substitution of one nucleotide for another.
Example showing a normal DNA sequence and a sequence with a substitution.
Original DNA: AAA ATG GAA GAG
Mutated DNA: AAA ATC GAA GAG
Deletion Mutation
A deletion mutation occurs when one or more nucleotides is/are lost from a DNA molecule.
Insertion Mutation
An insertion mutation occurs when one or more nucleotides is/are added to a DNA molecule.
Classes of Mutations
A silent mutation has a negligible effect on the organism because the resulting amino acid is identical.
Missense Mutations
A mutation that produces a protein with one different amino acid usually has a small to moderate effect on the protein overall.
For some proteins, such as hemoglobin, substitution of just one amino acid can result in the fatal disease sickle cell anemia.
Nonsense Mutations
If a mutation causes a big change, like producing a stop codon, the remainder of the protein will not be synthesized, which can have catastrophic results.
Genetic Diseases
Table summarizing characteristics of various genetic diseases:
Tay-Sachs disease: Mental retardation; caused by a defective hexosaminidase A enzyme
Sickle cell anemia: Anemia; occlusion and inflammation of blood capillaries, caused by defective hemoglobin
Phenylketonuria: Mental retardation; caused by a deficiency of the enzyme phenylalanine hydroxylase
Galactosemia: Mental retardation; caused by a deficiency of an enzyme needed for galactose metabolism
Huntington's disease: Progressive physical disability; caused by a defect in the gene that codes for the Htt protein
Viruses and Vaccines
A virus is an infectious agent consisting of a DNA or RNA molecule that is contained within a protein coating. It is incapable of replicating alone, so it invades a host organism and makes the host replicate the virus.
A vaccine is an inactive form of a virus that causes a person’s immune system to produce antibodies to the virus to ward off infection.