Telomeres

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
• RNA bonds leading strand
• 2) Forms template to
• extend leading strand

8

• Telomerase
• reverse transcriptase with attached RNA template
• 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 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 t1/2 10x, adding PEST drops
  t1/2 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 t1/2 10x, adding PEST drops
  t1/2 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 t1/2 10x, adding PEST drops
  t1/2 10x
• Sometimes targets poly-Ub
• Recent yeast study doesnt 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 t1/2 10x, adding PEST drops
  t1/2 10x
• Sometimes targets poly-Ub
• Recent yeast study doesnt 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.