Molecule of Inheritance - DNA

1. Molecule of Inheritance - DNA Ch 16

2. Morgan • Genes are on chromosomes • Chromosomes are made of DNA & protein • What is the molecule of inheritance?

3. What are genes made of?

4. 1928 - Transforming Factor • Frederick Griffith, a British medical officer, discovers that genetic information can be transferred from heat-killed bacteria cells to live ones, in a process called transformation.

5. Griffith’s Experiment - used pneumonia bacteria

6. 1944 - DNA is the inheritance molecule • Oswald Avery and his colleagues Maclyn McCarty and Colin MacLeod, repeat Griffith’s work, trying to identify which molecule is responsible for transformation. They identify Griffith's transforming agent as DNA.

7. Avery’s Experiment

8. 1952 • Alfred Hershey and Martha Chase experiment with the T2 virus, confirming that DNA is the genetic material (vs. protein).

9. What is the structure of DNA?

10. 1909, 1929 - Nucleotides • 1909 and 1929 - In 1909, Phoebus Levene discovered ribose, a sugar present in genetic material. Later in 1929, he discovered deoxyribose and nucleotides (adenine, guanine, cytosine, and thymine), recognizing the significance of phosphate-sugar bases in the structure of DNA.

11. DNA is made of nucleotides

12. 1949 - Base Pairing • Erwin Chargaff finds that the amount of adenine equals the amount of thymine, and the amount of guanine equals the amount of cytosine in DNA from every species. A = T, C = G

13. The two strands of the DNA molecule run antiparallel • One goes from 5’-3’, the complementary strand goes from 3’-5’

14. 1951 • Rosalind Franklin, Maurice Wilkins, and Raymond Gosling take X-ray diffraction pictures of DNA. From Rosalind Franklin’s pictures, she determines that DNA has a helical shape.

15. 1953 - Double Helix • James Watson and Francis Crick discover the double helix molecular structure of DNA.

16. What is the structure of the DNA molecule? • James Watson and Francis Crick • Built models of nucleotides • Determined how nucleotides were arranged in molecule: • Sugar phosphate backbone • Held together by Covalent bonds • Nitrogenous bases paired in middle – a purine is always paired with a pyrimidine • Held together by Hydrogen bonds

17. The DNA double helix is anti-parallel, which means that the 5' end of one strand is paired with the 3' end of its complementary strand (and vice versa).

18. 1962 • Francis Crick, James Watson, and Maurice Wilkins receive the Nobel Prize for determining the molecular structure of DNA. • In 1958, Rosalind Franklin died at age 37. The Nobel prize is not given posthumously.

19. James Watson about discovering the structure of DNA (video - 1:42 min) • http://www.hhmi.org/biointeractive/dna/video.html

20. DNA Replication • “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” • Watson & Crick • Replication – making DNA from existing DNA

21. Semiconservative replication – each daughter strand consists of an old strand (from parent molecule) and a newly made strand (Meselsohn-Stahl experiment) http://highered.mcgraw-hill.com/olc/dl/120076/bio22.swf

22. DNA replication

23. Energetics of DNA replication • Second law of thermodynamics – • Systems go towards more disorder DNA is creating order out of chaos, so does it go against the second law?

24. DNA + dNTP DNA (with new nucleotide) + P-P •  DNA (with new nucleotide ) + 2 P • Rather than adding nucleotides, DNA is synthesized from nucleoside triphosphates – a sugar + base + 3 phosphate groups • As they are added, the 2 phosphates are cleaved, and then split into two inorganic phosphates. • This is energetically favorable- an exergonic reaction coupled with the polymerization.

25. Directionality of DNA • DNA can only be synthesized in the 5’ – 3’ direction • Additional nucleotides are added to the 3’ end • This results in a problem when replicating DNA – one new strand can be synthesized continuously, the other has to be synthesized in segments

26. DNA replication fork: • http://highered.mcgraw-hill.com/olc/dl/120076/micro04.swf • How nucleotides are added to DNA strand: • http://highered.mcgraw-hill.com/olc/dl/120076/bio23.swf

27. Proteins involved in replication • Helicase – unwinds DNA • Primase – makes RNA primer (short sequence of 5-10 RNA bases) • Single strand binding proteins – hold DNA strands apart • DNA polymerase III – can only add to existing 3’ strand, adds nucleotides to 3’ end of DNA • Reads 3’-5’, builds 5’-3’

28. Proteins involved in replication • DNA polymerase I – removes RNA primer, replaces w/DNA • DNA ligase – joins ends of DNA from primer or Okazaki fragments • Topoisomerase – keeps DNA from rewinding

29. DNA replication • http://www.dnatube.com/video/335/Animated-DNA-Replication • DNA wrapping & replication http://www.youtube.com/watch?NR=1&feature=fvwp&v=OjPcT1uUZiE

30. Replication Bubble Replication occurs on either side - note leading & lagging strands

31. DNA repairs • Mismatch repair • http://www.youtube.com/watch?v=7xc1lmWDiS4

32. DNA damage

33. Thymine dimer http://vimeo.com/81294755 Nucleotide excision repair 

34. Telomeres & Telomerase • http://www.youtube.com/watch?v=AJNoTmWsE0s • Without Telomerase – cells reach limit of divisions, 50-70 • Telomerase found in embryonic cells, adult cells that need to divide regularly (i.e. male germ cells) – not in most somatic cells. • Telomerase activation has been found in 90% of tumors – cells are “immortal”, can divide forever. . .