telomeres special sequences at chromosome ends special proteins protect them
TRANSCRIPT
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• telomeres lose ~ 200 bp/S
Telomeres• can't copy 5' end of lagging strand since remove primer• telomeres lose ~ 200 bp / S• telomerase replaces them
Telomerase• telomeres lose ~ 200 bp / S• telomerase replaces themreverse transcriptase with attached RNA template
Telomerase• telomeres lose ~ 200 bp each S• telomerase replaces missing basesreverse transcriptase with attached RNA template1) RNA bonds leading strand
Telomerasereverse transcriptase with attached RNA
template1)RNA bonds leading strand2) Forms template to extend leading strand
Telomerasereverse transcriptase with attached RNA
template1)RNA bonds leading strand2) Forms template to extend leading strand3) Translocates6 bases & repeats
Telomerasereverse transcriptase with attached RNA
template1)RNA bonds leading strand2) Forms template to extend leading strand3) Translocates6 bases & repeats4) Extend lagging strandwith primer & DNA pol
TelomeresAging theory:” mature” cells lose telomerase
Telomeres
Aging theory:” mature” cells lose telomerase
lose DNA each S
Telomeres
Aging theory:” mature” cells lose telomerase
lose DNA each S
Die when lose too much
Telomeres
Aging theory:” mature” cells lose telomerase
lose DNA each S
Die when lose too much
Cancer cells reactivate telomerase
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
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
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
Regulating E3 ligasesThe COP9 signalosome (CSN), a complex of 8 proteins,
regulates E3 ligases by removing Nedd8 from cullin
Regulating E3 ligasesThe COP9 signalosome (CSN), a complex of 8 proteins,
regulates E3 ligases by removing Nedd8 from cullinCAND1 then blocks cullin
Regulating E3 ligasesThe COP9 signalosome (CSN), a complex of 8 proteins,
regulates E3 ligases by removing Nedd8 from cullinCAND1 then blocks cullinUbc12 replaces Nedd8
Regulating E3 ligasesThe COP9 signalosome (CSN), a complex of 8 proteins,
regulates E3 ligases by removing Nedd8 from cullinCAND1 then blocks cullinUbc12 replaces Nedd8Regulates DNA-damage response, cell-cycle & gene expression
Regulating E3 ligasesThe COP9 signalosome (CSN), a complex of 8 proteins,
regulates E3 ligases by removing Nedd8 from cullinCAND1 then blocks cullinUbc12 replaces Nedd8Regulates DNA-damage response, cell-cycle & gene expressionNot all E3 ligases associate withCullins!
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
COP1 is a non-cullin-associated E3 ligase• Recent data indicates that COP1 may also associate
with CUL4
Protein degradation rate varies 100xMost have motifs marking them for polyubiquitination:
taken to proteosome & destroyedOther 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
Protein degradation rate varies 100xOther 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
Protein degradation rate varies 100xOther 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
Protein degradation rate varies 100xOther 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
Protein degradation rate varies 100xOther 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.