1. Maintenance of genomes Copying the genome sequence Repairing damage to the genome sequence Rearranging genome sequences

2. Maintenance of genomes Copying the genome sequence = Replication

3. Replication is semiconservative after 1. replication after 2. replication

4. Figure 15.3a Genomes 3 (© Garland Science 2007) The Meselson-Stahl experiment

5. Replication is semiconservative after 1. replication after 2. replication

6. Replication Initiation DNA synthesis Termination

8. Origins of replication

9. Initiation of replication at oriC

10. Replication Initiation DNA synthesis Termination

11. DNA synthesis

12. Figure 15.13 Genomes 3 (© Garland Science 2007) 4-15 nt8-12 nt≈ 20 nt

13. Replication Initiation DNA synthesis Termination

14. DNA synthesis

17. DNA polymerases (active site)

20. DNA polymerases (exonuclease activity)

21. DNA synthesis

22. Figure 15.14 Genomes 3 (© Garland Science 2007) Topoisomerases resolve tension during DNA unwinding

23. Figure 15.16 Genomes 3 (© Garland Science 2007) Single strand binding proteins (SSBs) protect exposed single DNA strands

24. Figure 15.16 Genomes 3 (© Garland Science 2007)

25. Three DNA polymerase core proteins synthesize DNA simultaneously on the leading and lagging strand

26. In E. coli three DNA polymerase core proteins synthesize DNA simultaneously on the leading and lagging strand

27. Three DNA polymerase core proteins synthesize DNA simultaneously on the leading and lagging strand

28. Three DNA polymerase core proteins synthesize DNA simultaneously on the leading and lagging strand

29. Primer removal DNA polymerase I

30. Origins of replication

31. DnaA binding leads to strand separation A A A A A A A A A A A A A A DnaA-ATP ORC-ATP (Origin Recognition Complex) (6 proteins) ORC binding does not lead to strand separation

32. ORC recruits cdc6 and two helicases that encircle the double-stranded DNA Helicases

33. Helicase (Mcm2-7) activation

34. Helicases are activated only in S-phase of the cell cycle

35. DNA is replicated only once per cell cycle

36. In bacteria re-initiation is blocked by SeqA

37. Finishing replication in bacteria

38. Finishing replication in eukaryotes (The end replication problem)

39. Protein priming in some bacteria and viruses

40. Extension of the ends of eukaryotic chromosomes by telomerase

41. Telomere binding proteins regulate telomerase activity and telomere length S. cerevisiae humans

42. The telomeric ends of chromosomes are protected by proteins