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The Molecular Basis of Inheritance
Who are these two famous characters of science?
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Searching for Genetic Material
Mendel (1865): Inheritance
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Searching for Genetic Material
What are chromosomes made of? T.H. Morgan (1910): genes linked on chromosomes Chromosomes are made of DNA and proteins DNA and proteins are the two candidates for the genetic material
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Searching for Genetic Material
Griffith(1928): bacterial work- streptococcus pneumoniae
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Searching for Genetic Material
Griffiths’ conclusion: Transformation: change in genotype and phenotype due to assimilation of external substance (DNA) by a cell
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Searching for Genetic Material
Avery and team(MacLeod and McCarty)(1944): transformation agent was DNA
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Searching for Genetic Material
Hershey and Chase(1952): determine that DNA is the hereditary material and not proteins:
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DNA Structure Chargaff(1950): Chargaff rules: A= T, C= G
found “peculiar regularity” in the ratios of nucleotide bases within a single species: A = 30.3% T = 30.3% C= 19.9% G = 19.5% Chargaff rules: A= T, C= G
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Watson & Crick(Wilkins, Franklin)(1953):
The Double Helix
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The Double Helix: Basic Unit of Nucleic Acids = nucleotide
Sugar/ phosphate backbone Nitrogen base
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Sugar/phosphate backbone:
5 carbon sugar = ribose Phosphate group Phosphodiester bond
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Nitrogenous bases: In DNA there are four(make up the interior of the molecule): Adenine Thymine Cytosine Guanine Two groups: Purines: double ringed structures Adenine and Guanine Pyrimidines: single ringed structures Thymine and Cytosine
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Polynucleotide directionality:
5’ to 3’ 5’ with the phosphate group 3’ with the –OH group
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Double strands: Inward facing nitrogen base will pair with their complementary base A will pair with T (two H- bonds) G will pair with G (three H- bonds) A double ringed structure will always pair with a single ringed structure to maintain width.
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Antiparallel: DNA strands are oriented in the opposite directions
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Other forces: Van der Waals attractions play a role in holding the DNA molecule together
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The Double Helix:
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DNA Replication
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Watson and Crick: Proposed the semiconservative model of DNA replication:
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Meselson & Stahl: semiconservative replication
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Enzymes: Helicase, DNA polymerase, Primase, DNA ligase Topoisomerase
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http://highered. mcgraw- hill
hill.com/sites/ /student_view0/chapter3/a nimation__dna_replication__quiz_1_.html
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5. 2. 1. ?’ ?’ ?’ ?’ 4. 3.
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Replication Origin: Sites where DNA replication begins
Prokaryotes: one origin Replication proceeds in two directions Humans: hundreds maybe thousands of origins
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Replication bubbles and Replication Forks;
Replication bubble: unwinding and separation of the DNA strand Replication fork: Y- shaped region at each end of the bubble
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Strand elongation and directionality:
Elongation catalyzed by DNA polymerase E. coli bacteria adds nucleotides at a rate of 500/sec Humans add nucleotides at a rate of 50/sec Nucleoside triphosphate:
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Strand elongation and directionality
Antiparallel elonagation: 5’ – 3’ direction Leading strand Lagging strand Okazaki fragments E. coli fragments: nucleotides Human fragments:
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Primers: How many primers are needed for the leading strand?
How many primers are needed for the lagging strand?
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DNA Replication Continued:
DNA replication ensures continuity of hereditary information:
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DNA Replication continued:
1. Enzymes of DNA replication work as part of a large complex: 2. Replication process is probably a stationary process DNA polymerase “reels- in” the parent DNA Lagging strand may may be looped
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Problems with replication:
Incorrectly paired nucleotides Error rate: 1 out of every 100,000 base pairs DNA polymerase proof reads each nucleotide Incorrectly paired nucleotides are immediately removed and replaced 1 out of 10 billion
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Problems with replication:
Mismatch pair: Repaired by the action of nuclease(one of many different DNA repair enzymes) Removes nucleotides damaged by chemicals or the environment
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Problems with replication:
End replication repair:
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Telomeres and Telomerase:
Telomeres= nucleotide sequences at the ends of the DNA molecule Contain a repeated unit TTAGGG Do not contain genes No nucleotides added Protects the molecule from the replication process Triggers apoptosis May contribute to the aging process
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Telomerase: Catalyzes the lengthening of the telomeres in eukaryotic germ cells
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