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1. Introduction
2. Genome instability in tumor cells
3. The "Philadelphia chromosome"
4. Loss of heterozygosity (LOH)
5. Defects in repair of chromosome breaks
6. Double strand break (DSB) repair is essential
7. Talk outline
8. DSB can arise by replication over a ssDNA nick
9. Stalled replication forks may "break"
10. DSBs at "fragile sites"
11. Oncogene-induced DNA damage model
12. Programmed DSBs
13. Burkitt's lymphoma - common translocation
14. Homologous recombination mechanisms (1)
15. Replication fork regression
16. EM of regressed replication fork
17. Holliday junctions (HJ) - EM
18. HJ is a symmetric structure
19. HJ can branch migrate
20. RuvA and RubB drive branch migration
21. Branch migration in E.coli
22. HJ are "resolved" by enzymes (1)
23. HJ are "resolved" by enzymes (2)
24. Cleavage of a HJ at a stalled replication fork
25. Replication re-start by homologous recombination
26. Basic strand exchange (1)
27. Strand exchange - in vitro assays
28. Basic strand exchange (2)
29. Basic strand exchange (3)
30. X-ray crystallography of strand exchange
31. Resolution of remaining HJs
32. Sisters chromatids exchange (SCE)
33. DNA damage induces SCE events
34. Break induced replication (BIR)
35. BIR and telomerase
36. Homologous recombination mechanisms (2)
37. Single strand annealing
38. Single strand annealing can produce deletions
39. Homologous recombination mechanisms (3)
40. DNA repair by gene conversion
41. Bloom's syndrome
42. Synthesis-dependent strand annealing (SDSA)
43. Budding yeast as a model of SDSA
44. Observing DNA repair in real time
45. DSB repair process (1)
46. DSB repair process (2)
47. Visualizing Rad51 loading
48. Mutagenesis associated with gene conversion
49. Overview of DNA repair mechanisms
50. Nonhomologous end-joining pathways (NHEJ)
51. Ku- and Xrcc4-independent alternatives
52. NHEJ plays a major role in translocations
53. Changes in copy number in cancer cells
54. Gene amplification
55. Copy number variation involves recombination
56. Summary
57. Acknowledgements

Topics Covered

• Genome instability in tumor cells
• Mutations
• Loss of heterozygozity
• Repair of chromosome breaks
• Double-strand break repair is essential for life
• Replication stalling and fragile sites
• Programmed DSBs
• Repair of DSBs arising during DNA replication by recombination
• The homologous recombination machinery
• E. coli
• Holliday junctions
• Break-induce replication
• Single strand annealing
• Types of homologous recombination
• Observing DNA repair in real time
• Molecular studies of recombination
• Nonhomologous end-joining (NHEJ) pathways
• Copy number variation
• Gene amplification

Links

Series:

• Introduction to Human Genetics

Categories:

• Cell Biology
• Genetics & Epigenetics

Talk Citation

Publication History

• Published on December 28, 2009

Financial Disclosures

• Prof. James Haber has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.