1. Chapter 19 Nucleic Acids Nucleic acids represent the fourth major class of biomolecules (proteins, carbohydrates, fats)Nucleic acids represent the fourth major class of biomolecules (proteins, carbohydrates, fats) Like other Macromolecules- contain multiple similar monomeric units covalently joined to produce large polymers Ch 19 Nucleic Acids Ch 20 DNA Replication Ch 21 Transcription and RNA Processing Ch 22 Protein Synthesis Read the chapters

2. Chapter 19 Nucleic Acids Nucleic acids represent the fourth major class of biomolecules (proteins, carbohydrates, fats)Nucleic acids represent the fourth major class of biomolecules (proteins, carbohydrates, fats) Genome - the genetic information of an organismGenome - the genetic information of an organism 1889: Isolated acidic molecule from nuclei (nucleic acid) 1944: DNA is the mol that carries genetic information Oswald Avery 1953: Watson/Crick determine structure of DNA Like other Macromolecules- contain multiple similar monomeric units covalently joined to produce large polymers

3. 1953: James Watson and Francis Crick determine structure of DNA Feb. 28 th 1953: Eagle pub in Cambridge “we have found the secret of life”

4. Information specifying protein structure Information flow:Information flow: DNA RNAPROTEIN DNA RNAPROTEIN Transcription - copying of the DNA sequence information into RNATranscription - copying of the DNA sequence information into RNA Translation - Information in RNA molecules is translated during polypeptide chain synthesisTranslation - Information in RNA molecules is translated during polypeptide chain synthesis Reverse transcriptase (retro-viruses) F. Crick 1958: Central dogma

5. Nucleic acids are polynucleotidesNucleic acids are polynucleotides Nucleotides have three components: (1) A five-carbon sugar (2) A weakly basic nitrogen base (3) PhosphateNucleotides have three components: (1) A five-carbon sugar (2) A weakly basic nitrogen base (3) Phosphate Nucleotides Are the Building Blocks of Nucleic Acids Unsaturated (double bonds) Planar and absorb UV

6. Nucleotides have three components: five-carbon sugar weakly basic nitrogen base Phosphate Nucleotides Are the Building Blocks of Nucleic Acids What type of bond?

7. Nucleic acids are polynucleotides Nucleotides have three components: A five-carbon sugar A weakly basic nitrogen base Phosphate Nucleotides Are the Building Blocks of Nucleic Acids

8. Tautomeric forms in equilibrium Amino and Lactam (keto) forms more stable and predominate ketoenol

9. Fig 19.6 Fig 19.6 Hydrogen bond sites in nucleic acidsHydrogen bond sites in nucleic acids X

11. Nucleosides RNA

12. Nucleosides RNA DNA

13. Ribonucleosides contain threeRibonucleosides contain three hydroxyl groups (2’, 3’ and 5’) Deoxyribonucleosides can be phosphorylated at theDeoxyribonucleosides can be phosphorylated at the 3’ and 5’ positions Nucleotides A nucleotide is assumed to be 5’-phosphate unless specified otherwise AMP=pAATP=pppA phosphate esters of nucleosides Potential sites of phosphate:

14. Purine vrs Pyrimidine ThymineCytosineGuanine UracilAdenine

15. Purine vrs Pyrimidine ThymineCytosineGuanine UracilAdenine

16. Nucleoside vrs Nucleotide

17. Macromolecules Nucleoside vrs Nucleotide Tues Quiz: Know the difference between nucleoside/nucleotide, purine/pyrimidine Be able to identify and name the base structures (adenine etc) Name the nucleoside (adenosine etc)

19. Anti form predominates

20. Nucleotides joined by 3’-5’ phosphodiester linkages

21. The Free Energy of ATP Phosphoanhydride vrs Phosphoester linkage

22. Structure of the tetranucleotide pdApdGpdTpdC Nucleotides joined by 3’-5’ phosphodiester linkages Primary structure Extended conformation Long and thin Directionality 5’-3’ Backbone: phosphate and 3’,4’ and 5’ carbon and 3’ oxygen

23. Erwin Chargaff: Chargaff rules: A and T are present in equal amounts in DNA Ratio of purine/pyrimidine always 1:1 DNA is double stranded and A pairs with T (and C with G) Same with G and C A=T DNA Is Double-Stranded G=C Watson and Crick used all the data---- double helix DNA structure

24. Two strands run in opposite directions Bases in opposite strands pair by complementary hydrogen bonding Adenine (A) - Thymine (T) Guanine (G) - Cytosine (C) Two Antiparallel Strands Form a Double Helix Complementary: Complementary: can serve as template For other strand Equal distance between backbone (Purine/pyrimidine 1:1)

25. Complementary base pairing and stacking in DNAComplementary base pairing and stacking in DNA Stacking of bases Stabilizes dsDNA Cooperativenon-covalent Within hydrophobic interior Helix allows effective stacking

26. Three dimensional structure of DNA A double helix has two grooves of unequal width: major groove and minor grooveA double helix has two grooves of unequal width: major groove and minor groove Within each groove base pairs are exposed and are accessible to interactions with other moleculesWithin each groove base pairs are exposed and are accessible to interactions with other molecules DNA-binding proteins can use these interactions to “read” a specific sequenceDNA-binding proteins can use these interactions to “read” a specific sequence B-DNA is a right-handed helix, diam. = 2.37nm Rise (distance between stacked bases) =0.33nmRise (distance between stacked bases) =0.33nm Pitch (distance to complete one turn) = 3.40 nmPitch (distance to complete one turn) = 3.40 nm 10.4 base pairs per turn10.4 base pairs per turn Structure of helix allows access to info

27. Two alternative structures to B-DNA: A-DNA (forms when DNA is dehydrated) Z-DNA (when certain sequences are present) A-DNA is more tightly wound than B-DNA, and has grooves of similar width Z-DNA has no grooves and a left-handed helix Both A-DNA and Z-DNA exist in vivo in short regions of DNA A B Z Conformations of Double-Stranded DNA G/C rich regions dG residue: base is in Syn conformation

28. Race to determine the structure of DNA Watson and Crick model 1953 DATA: Chargaff rules ; A=T and G=C Card board cut out puzzle Proper tautomeric forms of bases What data did they collect on their own ????? 1944 realized DNA carried genetic info 1947 Crick knew no biology, little organic chemistry or crystallography 1951 met Watson 1953 determined structure of DNA 1954 finished PhD on X-ray diffraction of proteins 1962 Nobel prize Evidence for helical nature

29. Race to determine the structure of DNA “Photo 51” Rosalind Franklin Watson and Crick model 1953 Linus Pauling----wrong !! 1953 paper incorrect triple helical model 1951 same triple helical model thrown out by W/C Rosalind tore it apart…it ignored her data 1951 solved alpha helix Diff sizes of bases—had to be on outside Did not have good x ray data—Wilkins turned him down How to pack neg charge in center? 10x more water in molecule than the model would allow Did not visit Franklin Two-fold symmetry (not triple) Cross-like reflections of helix

30. Rosalind Franklin Dies 1958 (ovarian cancer) Nobel prize 1962

31. Linus Pauling----wrong !!