1. Telomeres special sequences at chromosome ends special proteins protect them

2. Telomeres special sequences at chromosome ends special proteins protect them can't copy 5' end of lagging strand since remove primer

3. Telomeres can't copy 5' end of lagging strand since remove primer telomeres lose ~ 200 bp/S

4. Telomeres can't copy 5' end of lagging strand since remove primer telomeres lose ~ 200 bp / S telomerase replaces them

5. Telomerase telomeres lose ~ 200 bp / S telomerase replaces them reverse transcriptase with attached RNA template

6. Telomerase telomeres lose ~ 200 bp each S telomerase replaces missing bases reverse transcriptase with attached RNA template 1) RNA bonds leading strand

7. Telomerase reverse transcriptase with attached RNA template 1) RNA bonds leading strand 2) Forms template to extend leading strand

8. Telomerase reverse transcriptase with attached RNA template 1) RNA bonds leading strand 2) Forms template to extend leading strand 3) Translocates 6 bases & repeats

9. Telomerase reverse transcriptase with attached RNA template 1) RNA bonds leading strand 2) Forms template to extend leading strand 3) Translocates 6 bases & repeats 4) Extend lagging strand with primer & DNA pol

10. Telomeres Aging theory:” mature” cells lose telomerase

11. Telomeres Aging theory:” mature” cells lose telomerase lose DNA each S

12. Telomeres Aging theory:” mature” cells lose telomerase lose DNA each S Die when lose too much

13. Telomeres Aging theory:” mature” cells lose telomerase lose DNA each S Die when lose too much Cancer cells reactivate telomerase

14. Telomeres Aging theory:” mature” cells lose telomerase lose DNA each cell cycle Die when lose too much Cancer cells reactivate telomerase [serum telomerase] can diagnose cancer

15. Telomeres Aging theory:” mature” cells lose telomerase lose DNA each S Die when lose too much Cancer cells reactivate telomerase [serum telomerase] can diagnose cancer Inhibiting telomerase kills cancer cells

16. Telomeres Aging theory:” mature” cells lose telomerase lose DNA each S Die when lose too much Cancer cells reactivate telomerase [serum telomerase] can diagnose cancer Inhibiting telomerase kills cancer cells Telomerase is symptom cf cause of cancer

17. Regulating E3 ligases The COP9 signalosome (CSN), a complex of 8 proteins, regulates E3 ligases by removing Nedd8 from cullin

18. Regulating E3 ligases The COP9 signalosome (CSN), a complex of 8 proteins, regulates E3 ligases by removing Nedd8 from cullin CAND1 then blocks cullin

19. Regulating E3 ligases The COP9 signalosome (CSN), a complex of 8 proteins, regulates E3 ligases by removing Nedd8 from cullin CAND1 then blocks cullin Ubc12 replaces Nedd8

20. Regulating E3 ligases The COP9 signalosome (CSN), a complex of 8 proteins, regulates E3 ligases by removing Nedd8 from cullin CAND1 then blocks cullin Ubc12 replaces Nedd8 Regulates DNA-damage response, cell-cycle & gene expression

21. Regulating E3 ligases The COP9 signalosome (CSN), a complex of 8 proteins, regulates E3 ligases by removing Nedd8 from cullin CAND1 then blocks cullin Ubc12 replaces Nedd8 Regulates DNA-damage response, cell-cycle & gene expression Not all E3 ligases associate with Cullins!

22. COP1 is a non-cullin-associated E3 ligase Protein degradation is important for light regulation COP1/SPA1 tags transcription factors for degradation W/O COP1 they act in dark In light COP1 is exported to cytoplasm so TF can act

23. COP1 is a non-cullin-associated E3 ligase Recent data indicates that COP1 may also associate with CUL4

24. Protein degradation rate varies 100x Most have motifs marking them for polyubiquitination : taken to proteosome & destroyed Other signals for selective degradation include PEST & KFERQ PEST : found in many rapidly degraded proteins e.g. ABCA1 (which exports cholesterol in association with apoA-I) is degraded by calpain

25. Protein degradation rate varies 100x Other signals for selective degradation include PEST & KFERQ PEST : found in many rapidly degraded proteins e.g. ABCA1 (which exports cholesterol in association with apoA-I) is degraded by calpain Deletion increases t 1/2 10x, adding PEST drops t 1/2 10x

26. Protein degradation rate varies 100x Other signals for selective degradation include PEST & KFERQ PEST : found in many rapidly degraded proteins e.g. ABCA1 (which exports cholesterol in association with apoA-I) is degraded by calpain Deletion increases t 1/2 10x, adding PEST drops t 1/2 10x Sometimes targets poly-Ub

27. Protein degradation rate varies 100x Other signals for selective degradation include PEST & KFERQ PEST : found in many rapidly degraded proteins e.g. ABCA1 (which exports cholesterol in association with apoA-I) is degraded by calpain Deletion increases t 1/2 10x, adding PEST drops t 1/2 10x Sometimes targets poly-Ub Recent yeast study doesn’t support general role

28. Protein degradation rate varies 100x Other signals for selective degradation include PEST & KFERQ PEST : found in many rapidly degraded proteins e.g. ABCA1 (which exports cholesterol in association with apoA-I) is degraded by calpain Deletion increases t 1/2 10x, adding PEST drops t 1/2 10x Sometimes targets poly-Ub Recent yeast study doesn’t support general role KFERQ: cytosolic proteins with KFERQ are selectively taken up by lysosomes in chaperone-mediated autophagy under conditions of nutritional or oxidative stress.