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The Molecular Basis of Inheritance

The Molecular Basis of Inheritance. Chapter 16. Sisters of Loretto’s Chapel in 1853. The Miraculous Staircase at Loretto Chapel in New Mexico. The Miraculous Staircase and the structure of DNA are amazingly similar. Both have about 10 bases (stairs) per turn

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The Molecular Basis of Inheritance

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  1. The Molecular Basis of Inheritance Chapter 16

  2. Sisters of Loretto’s Chapel in 1853

  3. The Miraculous Staircase at Loretto Chapel in New Mexico

  4. The Miraculous Staircase and the structure of DNA are amazingly similar. • Both have about 10 bases (stairs) per turn • Distance in between one railing (backbone in DNA) and another are of the same scaling as in the DNA helix. • The axis of the turns of the staircase is 36 degrees, andn the fiber axis in the DNA helix is 36 degrees.

  5. 2. Discovery of DNA structure Chargaff Franklin Watson & Crick

  6. Watson & Crick built models until they got the right structure

  7. Chargaff What do the data show?

  8. Rosalind Franklin X-ray crystallography  DNA is a helix  DNA has a constant diameter

  9. Antiparallel strands 3’ end -OH (hydroxyl) group attached to the 3’carbon of the sugar 5’ end  phosphate attached to 5’ carbon of the last nucleotide

  10. DNA • Topics: • 1. Science as a process: evidence for DNA as genetic material • Griffith • Avery • Hershey and Chase • 2. Discovery of the double helix: • Rosalind Franklin • Watson & Crick • 3. DNA replication • 4. DNA repair

  11. 1928  Griffith – Streptococcus pneumoniae - transformation

  12. Mouse Dead Mouse alive Mouse alive Mouse alive Mouse alive 1944  Avery transforming agent is DNA

  13. 1952 Alfred Hershey and Martha Chase

  14. One of the most famous sentences in a science paper ever! • “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” -Watson, J. D. and Crick, F.H.C., Nature, 171, p.737-8, (1953).

  15. The Meselson-Stahl experiment

  16. The Meselson-Stahl experiment Late 50’s

  17. 3 Semi-conservative model Nucleosides tri-phosphate 50 nucleotides per second

  18. Enzyme that adds new nucleotides DNA polymerase Energy for polymerization  Nucleotides are actually nucleosides triphosphates Nucleosides triphosphate are REACTIVE (=unstable) When they join the DNA strand, two P are lost Exergonic reaction of the two P breaking apart drives polymerization

  19. http://www.ncc.gmu.edu/dna/repanim.htm The replication fork moves in one direction, but DNA replication only goes in the 5' to 3' direction. This paradox is resolved by the use of Okazaki fragments. Then  DNA ligase joins the fragments together http://www.nobel.se/medicine/educational/dna/a/replication/lagging_ani.html

  20. Other enzyme: • RNA Primase: makes the initial stretch (about 10 nucleotides) Initial stretch is RNA! • One RNA primer only needed for leading strand • Many (one per fragment) required for lagging strand. Video Clip 1 Video Clip 2 Video Clip 3

  21. 4. DNA REPAIR • MISTAKES • DNA polymerase “proofreads” • Otherwise: nucleotide excision repair • polymerase • ligase

  22. Telomeres = end sequences of chromosomes. Are non-coding The end-replication problem There is no way to complete the 5’ end of a daughter DNA molecule Telomerase enzyme that patches up the 5’ end How, if there is no DNA to copy from? Has a small piece of RNA, and uses it as template

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