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The Molecular Basis of Inheritance

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1 The Molecular Basis of Inheritance
Who are these two famous characters of science?

2 Searching for Genetic Material
Mendel (1865): Inheritance

3 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

4 Searching for Genetic Material
Griffith(1928): bacterial work- streptococcus pneumoniae

5 Searching for Genetic Material
Griffiths’ conclusion: Transformation: change in genotype and phenotype due to assimilation of external substance (DNA) by a cell

6 Searching for Genetic Material
Avery and team(MacLeod and McCarty)(1944): transformation agent was DNA

7 Searching for Genetic Material
Hershey and Chase(1952): determine that DNA is the hereditary material and not proteins:

8 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

9 Watson & Crick(Wilkins, Franklin)(1953):
The Double Helix

10 The Double Helix: Basic Unit of Nucleic Acids = nucleotide
Sugar/ phosphate backbone Nitrogen base

11 Sugar/phosphate backbone:
5 carbon sugar = ribose Phosphate group Phosphodiester bond

12 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

13 Polynucleotide directionality:
5’ to 3’ 5’ with the phosphate group 3’ with the –OH group

14 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.

15

16 Antiparallel: DNA strands are oriented in the opposite directions

17 Other forces: Van der Waals attractions play a role in holding the DNA molecule together

18 The Double Helix:

19 DNA Replication

20 Watson and Crick: Proposed the semiconservative model of DNA replication:

21 Meselson & Stahl: semiconservative replication

22 Enzymes: Helicase, DNA polymerase, Primase, DNA ligase Topoisomerase

23 http://highered. mcgraw- hill
hill.com/sites/ /student_view0/chapter3/a nimation__dna_replication__quiz_1_.html

24 5. 2. 1. ?’ ?’ ?’ ?’ 4. 3.

25 Replication Origin: Sites where DNA replication begins
Prokaryotes: one origin Replication proceeds in two directions Humans: hundreds maybe thousands of origins

26 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

27 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:

28 Strand elongation and directionality
Antiparallel elonagation: 5’ – 3’ direction Leading strand Lagging strand Okazaki fragments E. coli fragments: nucleotides Human fragments:

29 Primers: How many primers are needed for the leading strand?
How many primers are needed for the lagging strand?

30 DNA Replication Continued:
DNA replication ensures continuity of hereditary information:

31 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

32 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

33 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

34 Problems with replication:
End replication repair:

35 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

36 Telomerase: Catalyzes the lengthening of the telomeres in eukaryotic germ cells


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