1. How to prevent and cure cancer and live forever
Cellular repair of DNA damage, prevention of damage and how cells become immortal

2. DNA MUTATIONS CAN RESULT FROM INCORRECT MATCHING OF BASE PAIRS
H lost off N on Cytosine
H lost off N on Guanine
Error rate due to insertion of incorrect base pair by DNA polymerase is approximately 1 in 104.

3. DNA MUTATIONS CAN RESULT FROM INCORRECT MATCHING OF BASE PAIRS
TAUTOMERIC PROTON SHIFTS
Link to insertion mutation animation.

4. DNA POLYMERASE REDUCES ERRORS BY PROOFREADING (MISMATCH REPAIR)

5. DNA POLYMERASE PROOFREADING (MISMATCH REPAIR) REDUCES ERROR RATE TO 1 IN 108 BASES
Link to proofreading animation

6. PROOFREADING ANIMATION

7. How does cell know which is parent strand in mismatch repair?
In some cases original parent strand is chemically “marked” by methyl groups. In some cases the enzymes are forced to “guess” and guess wrong.
Link to methylation mismatch repair
NOT ON TEST

8. DNA MUTATIONS ARE CAUSED EXPOSURE TO RADIATION, CHEMICAL AND INFECTIOUS AGENTS SUCH AS VIRUSES OR CERTAIN BACTERIA
MUTATIONS IN DNA REPAIR SYSTEM ENZYMES, INCLUDING TUMOR SUPRESSION AND APOPTOSIS GENES GREATLY INCREASES CANCER RISK

9. Figure 16.17 Nucleotide excision repair of DNA damage
EXCISION REPAIR -REMOVE AND REPLACE DAMAGED DNA SECTION
ON TEST
Note repair enzymes:
Link to Thymine dimer repair animation

10. Ends Replication Problem
Problem of copying the 3’ parent end (lagging strand) in eukaryotes
Link to summanas video

11. 3’ 5’ OH 3’ 5’ OH 5’ 3’ OH 5’ 3’ OH 5’ 3’ 5’ 3’
LAGGING STRAND SYNTHESIS AT 3’ PARENT END
DNA POL I
Daughter Leading
Strand DNA 3’ 5’ OH 3’ 5’ OH 5’ 3’ OH 5’ 3’ OH 5’ 3’ 5’ 3’
Parent Strand

12. 3’ 5’ OH 3’ 5’ OH 5’ 3’ OH 3’ 5’ OH 5’ 3’ OH 5’ 3’ 5’ 3’
LAGGING STRAND SYNTHESIS AT 3’ PARENT END
DNA POL I
Daughter Leading
Strand DNA 3’ 5’ OH 3’ 5’ OH 5’ 3’ OH 3’ 5’ OH 5’ 3’ OH 5’ 3’ 5’ 3’
Parent Strand

13. LAGGING STRAND SYNTHESIS AT 3’ PARENT END
DNA POL I
Daughter Leading
Strand DNA 3’ 5’ OH 5’ 3’ 5’ 3’
Parent Strand
Since DNA polymerase I needs a template to bind to and an existing strand to elongate, there is a gap in the daughter strand opposite the 3’ parent strand that cannot be filled.

14. DNA polymerase I removes RNA primer
Fig 5
Ends of parental DNA strands
Leading strand
Lagging strand
DNA polymerase I removes RNA primer 3
Last fragment
Previous fragment
RNA primer
Lagging strand 5 3
Parental strand
Removal of primers and replacement with DNA where a 3 end is available
DNA Pol I cannot add to 5’ end, only 3’ end 5 3
Second round of replication
1 daughter is shortened and 1 has 3’ overhang in next round of replication 5
New leading strand 3
New lagging strand 5 3
Further rounds of replication
Shorter and shorter daughter molecules

15. Replication in Eukaryotes occurs at multiple origin points within the DNA but never at the ends; Process of lagging strand synthesis results in incomplete ends on 3’ parent ends of chromosome

16. TELOMERES ARE NONSENSE REPEAT SEQUENCES ATTACHED TO ENDS OF CHROMOSOMES THAT CAN BE SHORTENED WITHOUT DAMAGING CODING REGIONS OF CHROMOSOMES.
Video link
Human telomeres are approximately 2000 bp in length (≈330 TTAGGG repeats); Cells can undergo about divisions before chromosome damage causes death

17. Link to Telomere animation
Elizabeth Blackburn
Carol Grei
Shared 2009 Nobel Prize in Medicine for discovery of telomeres (along with Jack W. Szostak)

18. Figure 16.19b Telomeres and telomerase

19. Figure 16.19b Telomeres and telomerase

20. Addition of telomeres is catalyzed by enzyme telomerase
Link to telomere animation

23. Eternal Life from expression of telomere genes?
In theory, our cells could continue to divide indefinitely if the telomere gene which is not normally expressed in adult cells could be switched on.
The experiment has been tried in mice. It does extend health and life, in one Harvard study it actually seem to reverse some aging processes. In Humans increasing telomerase activity is high associated with increased cancer risk.

24. Stem cells and cancer have active telomerase; Differentiated cells do not express telomerase gene

25. Telomerase Inhibitors are potential anti-cancer drugs
Cancer cells are cells with rapid, uncontrolled replication.
Cancer cells apparently can undergo unlimited cell divisions.
Rate of Growth of Tumors could be slowed by telomerase inhibitors ; after many generations cancer cells would eventually die after telomeres become too short.
Note: Telomeres in cancer cells are typically shorter than those in normal cells.