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Telomeres special sequences at chromosome ends special proteins protect them

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

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Telomeres special sequences at chromosome ends special proteins protect them

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  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 RNAtemplate • 1) RNA bonds leading strand

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

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

  9. Telomerase reverse transcriptase with attached RNA template 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 degradationrate 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 degradationrate 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 t1/2 10x, adding PEST drops t1/2 10x

  26. Protein degradationrate 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 t1/2 10x, adding PEST drops t1/2 10x • Sometimes targets poly-Ub

  27. Protein degradationrate 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 t1/2 10x, adding PEST drops t1/2 10x • Sometimes targets poly-Ub • Recent yeast study doesn’t support general role

  28. Protein degradationrate 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 t1/2 10x, adding PEST drops t1/2 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.

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