1. DNA DNA = DeoxyriboNucleic AcidDNA = DeoxyriboNucleic Acid –Short nucleic acid –A polymer that stores genetic information –Found in the chromosomes of all organisms –Controls production of proteins depending on sequence of nitrogen bases –Unit of structure = nucleotide

2. DNA Nucleotide – 3 partsNucleotide – 3 parts 1.A sugar – deoxyribose 2.A phosphate group – PO 4 3.A nitrogen base Draw the Picture

3. Nitrogen Bases Nitrogen Bases – name source for the nucleotidesNitrogen Bases – name source for the nucleotides 2 different types:2 different types: –Purines – double ring AdenineAdenine GuanineGuanine –Pyrimidines – single ring CytosineCytosine ThymineThymine

4. Nitrogen Bases PurinesPyrimidines AdenineGuanine CytosineThymine Phosphate group Deoxyribose

5. DNA Structure Double Helix (twisting ladder) modeled by Watson & Crick 1953 Sides/backbone - alternating deoxyribose sugar & phosphate “Rungs” - nitrogen bases held together by hydrogen bonds

6. Base Pairing Base Pairing According to Chargaff’s Rule The complementary bases always pair a certain purine with a certain pyrimidine Base Base A = adenine A = adenine T = thymine T = thymine C = cytosine C = cytosine G = guanine G = guanine Complementary Base thymine thymineadenineguaninecytosine

7. Base Pairing Rule: –A always pairs with T –C always pairs with G Hydrogen bonds Nucleotide Sugar-phosphate backbone Key Adenine (A) Thymine (T) Cytosine (C) Guanine (G)

8. Chromosomes Prokaryotes 1.DNA is found in the cytoplasm 2.Single circular DNA molecules 3.DNA replication begins at a single point in the chromosome & proceeds in both directions until the chromosome is replicated Eukaryotes 1.Found in the nucleus 2.Chromosome number varies between species 3.DNA replication occurs at hundreds of places called replication forks

9. Replication – General Info The exact copying of DNAThe exact copying of DNA DNA must be copied before cells divide  each daughter cell has a complete set of DNADNA must be copied before cells divide  each daughter cell has a complete set of DNA Original strands serve as templates for new strandsOriginal strands serve as templates for new strands Replication occurs in both directionsReplication occurs in both directions

11. Enzymes in DNA replication Helicase unwinds parental double helix Binding proteins stabilize separate strands DNA polymerase III binds nucleotides to form new strands Ligase joins Okazaki fragments and seals other nicks in sugar- phosphate backbone Primase adds short primer to template strand DNA polymerase I (Exonuclease) removes RNA primer and inserts the correct bases

12. Binding proteins prevent single strands from rewinding. Helicase protein binds to DNA sequences called origins and unwinds DNA strands. 5’ 3’ 5’ 3’ Primase protein makes a short segment of RNA complementary to the DNA, a primer. 3’ 5’ 3’ Replication

13. Overall direction of replication 5’ 3’ 5’ 3’ 5’ 3’ 5’ DNA polymerase enzyme adds DNA nucleotides to the RNA primer. Replication

14. DNA polymerase enzyme adds DNA nucleotides to the RNA primer. 5’ Overall direction of replication 5’ 3’ 5’ 3’ DNA polymerase proofreads bases added and replaces incorrect nucleotides. Replication

15. 5’ 3’ 5’ 3’ 5’ 3’ Overall direction of replication Leading strand synthesis continues in a 5’ to 3’ direction. Replication

16. 3’ 5’ 3’ 5’ 3’ 5’ 3’ Overall direction of replication Okazaki fragment Leading strand synthesis continues in a 5’ to 3’ direction. Discontinuous synthesis produces 5’ to 3’ DNA segments called Okazaki fragments. Replication

17. 5’ 3’ 5’ 3’ 5’ 3’ Overall direction of replication 3’ Leading strand synthesis continues in a 5’ to 3’ direction. Discontinuous synthesis produces 5’ to 3’ DNA segments called Okazaki fragments. Okazaki fragment Replication

18. 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ Leading strand synthesis continues in a 5’ to 3’ direction. Discontinuous synthesis produces 5’ to 3’ DNA segments called Okazaki fragments. Replication

19. 3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ Leading strand synthesis continues in a 5’ to 3’ direction. Discontinuous synthesis produces 5’ to 3’ DNA segments called Okazaki fragments. Replication

20. 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’ Exonuclease activity of DNA polymerase I removes RNA primers. Replication

21. Polymerase activity of DNA polymerase I fills the gaps. Ligase forms bonds between sugar-phosphate backbone. 3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’ Replication

22. Replication Fork Overview

23. Proofreading DNA must be faithfully replicated…but mistakes occur –DNA polymerase (DNA pol) inserts the wrong nucleotide base in 1/10,000 bases DNA pol has a proofreading capability and can correct errors –Mismatch repair: ‘wrong’ inserted base can be removed –Excision repair: DNA may be damaged by chemicals, radiation, etc. Mechanism to cut out and replace with correct bases

24. Mutations A mismatching of base pairs, can occur at a rate of 1 per 10,000 bases. DNA polymerase proofreads and repairs accidental mismatched pairs. Chances of a mutation occurring at any one gene is over 1 in 100,000 Because the human genome is so large, even at this rate, mutations add up. Each of us probably inherited 3-4 mutations!

25. Proofreading and Repairing DNA DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides In mismatch repair of DNA, repair enzymes correct errors in base pairing In nucleotide excision DNA repair nucleases cut out and replace damaged stretches of DNA Nuclease DNA polymerase DNA ligase A thymine dimer distorts the DNA molecule. 1 A nuclease enzyme cuts the damaged DNA strand at two points and the damaged section is removed. 2 Repair synthesis by a DNA polymerase fills in the missing nucleotides. 3 DNA ligase seals the Free end of the new DNA To the old DNA, making the strand complete. 4

26. Accuracy of DNA Replication The chromosome of E. coli bacteria contains about 5 million bases pairs –Capable of copying this DNA in less than an hour The 46 chromosomes of a human cell contain about 6 BILLION base pairs of DNA!! –Printed one letter (A,C,T,G) at a time…would fill up over 900 volumes of Campbell. –Takes a cell a few hours to copy this DNA –With amazing accuracy – an average of 1 per billion nucleotides

27. Review of The Genetic Code The sequence of nitrogen bases (A,T,C & G) along a DNA strand code for the synthesis (making) of specific proteins. According to Chargaff’s Rule: –A bonds with T –C bonds with G

28. outsideProteins are made in the ribosomes outside the nucleus. DNA is copied (replicated) in the nucleus but cannot leave the nucleus. THEREFORE……. A message must be sent to the ribosomes in the cytoplasm telling them what proteins to make. This message is carried by a nucleic acid called messenger (mRNA ).

29. RNA Structure 1.RNA is a single strand 2.RNA has the sugar ribose 3.Adenine bonds with Uracil (NOT thymine). RNA differs from DNA in 3 ways:

30. Differences Between DNA Deoxyribose Sugar Double Stranded A, C, T, G Remains in nucleus RNA Ribose sugar Single Stranded A, C, U, G Moves out of nucleus