1. Nucleic Acids The blueprints

2. Types of Molecules Polymers of nucleotides DNA: code for genetic information RNA –mRNA intermediates in protein synthesis –rRNA carry out protein synthesis –tRNA translate info on mRNA into a.a. Gene

3. Nucleotide Components Bases + sugar + phosphate Bases –purine adenine guanine –pyrimidines thymine cytosine uracil

4. Bases

5. Nucleotide Components Sugars –ribose –Deoxyribose –Rings numbered using primes C1 = 1’ etc PO 4 3-

6. Nucleotide Structure Base-sugar-phosphate Base attached to C1 of sugar –Note sugar is β Phosphate attached to C5 of sugar Usually nucleotides are triphosphates, but can be mono or di

7. Nucleic Acid, a polymer of nucleotides

8. Nucleic Acids Polymer of nucleotides Phosphodiester linkage –3’ of one sugar to 5’ of other –vectorial Sequence read 5’ -  3’ Previous slide is C-A-A Next slide (a cartoon drawing) is A-T-G-C

9. Phosphodiester Bond

10. Chain elongation 3’ hydroxyl on chain has unshared pair on oxygen –attacks phosphorus on first phosphate of new nucleotide –Nucleophilic attack Driven by hydrolysis of PPi

11. Chain elongation

12. Base pairs –Bases are planar sp 2 hybridization Bases nonpolar – In Nucleic acids, there is base pairing –Complementarity Purines always base-pair with pyrimidines –Cytosine hydrogen bonds with guanine –Thymine hydrogen bonds with adenine or uracil Due to distancing and proximity of unshared pairs and hydrogens

13. GC base pair

14. AT base Pair

15. A-U base Pair (RNA)

16. Base Pairs (Cartoon drawing)

17. Complementarity One strand is complementary to the other If know sequence of one, can deduce that of the other –Templates –Implications in copying

18. DNA structure Double helix http://sbchem.sunys b.edu/msl/dna.gif

19. DNA structure B-DNA is most common Antiparallel bases inside –Hydrophobic –Perpendicular to helix stands complementary –Very important for information transfer –Each strand a template for the other. right handed major and minor groove

20. Other forms of DNA Z - DNA left handed; structure not fully understood A- DNA; tighter helix

21. DNA Types B- DNA (most common) http://images.google.com/imgres?imgurl=http://gibk26.bse.kyutech.ac.jp/jouhou/image/nucleic/dna/dna_st.small.gif& imgrefurl=http://gibk26.bse.kyutech.ac.jp/jouhou/image/nucleic/dna/dna.html&h=306&w=375&sz=32&hl=en&start= 32&tbnid=muC9F_v90eYO7M:&tbnh=100&tbnw=122&prev=/images%3Fq%3DA%2BDNA%26start%3D20%26nd sp%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN

22. A-DNA (supercoiled) http://images.google.com/imgres?imgurl=http://gibk26.bse.kyutech.ac.jp/jouhou/image/nucleic/dna/dna_st.small.gif&imgrefurl=http://gibk26. bse.kyutech.ac.jp/jouhou/image/nucleic/dna/dna.html&h=306&w=375&sz=32&hl=en&start=32&tbnid=muC9F_v90eYO7M:&tbnh=100&tb nw=122&prev=/images%3Fq%3DA%2BDNA%26start%3D20%26ndsp%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN

23. Z-DNA http://images.google.com/imgres?imgurl=http://gibk26.bse.kyutech.ac.jp/jouhou/image/nucleic/dna/dna_st.small.gif&imgrefurl=http://gibk26. bse.kyutech.ac.jp/jouhou/image/nucleic/dna/dna.html&h=306&w=375&sz=32&hl=en&start=32&tbnid=muC9F_v90eYO7M:&tbnh=100&tb nw=122&prev=/images%3Fq%3DA%2BDNA%26start%3D20%26ndsp%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN

24. Look down Axis http://www.accelrys.com/reference/gallery/life/dna.gif

25. Sequence dependent structures palindromes hairpins inverted repeats mirror repeats

26. RNA codes for protein no consistent secondary structure single stranded Ribose instead of deoxyribose Thymine (T) replaced by Uracil

27. RNA

28. Transfer RNA http://www.mie.utoronto.ca/labs/lcdlab/biopic/fig/12.07.jpg

29. Instability of RNA RNA unstable due to reactivity of 2’ hydroxyl on ribose Very labile DNA extremely stable

30. Nucleic Acid Chemistry Denaturation –unzip by heating –reannealing –CoT curves: more GC=higher temp Uses of DNA to find sequences –probes –forensic

31. DNA probes Take DNA from crime scene DNA from suspect, random other person etc See what matches

32. Nucleic Acid Chemistry Mutations –changes in sequence/structure –nonenzymatic changes thymine dimers deamination oxidative damage

33. Nucleic Acid Chemistry http://www.dnalc.org/resources/BiologyAni mationLibrary.htm Sequencing PCR Southern Blotting Probes

34. DNA sequencing, Sanger dideoxy method 4 samples Each gets template and nucleotides –One dideoxy nucleotide –Has no 3’ OH so chain can’t elongate Sample 1 –ddTTP…stops at T Sample 2 –ddATP…stops at A Sample 3 –ddCTP…stops at C Sample 4 –ddGTP…stops at G Run on Gel –Read from bottom up

35. Sample Sanger Gel

36. Human Genome Project http://www.ornl.gov/sci/techresources/Hum an_Genome/home.shtml