Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Functional Ageing > Telomeres and Telomerase > Flashcards

Telomeres and Telomerase Flashcards

1
Q

What do telomeres do?

A

cap eukaryotic chromosomes at each end to maintain integrity and stability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What part of DNA are telomeres associated with?

A

the non-coding part

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What do telomeres prevent chromosomes from doing?

A

fusing with each other to produce abnormal chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What happens in telomere restriction fragment analysis?

A

genomic DNA samples (specifically metaphase chromosomes) are digested with restriction enzymes, leaving behind telomere DNA repeats and some sub-telomeric DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is telomerase?

A

a large ribo-nucleoprotein that includes an RNA template and a catalytic protein component; essentially a reverse transcriptase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is a reverse transcriptase?

A

a DNA polymerase that synthesises DNA using an RNA template

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Where is telomerase present and when it is activated?

A

present in G1 but activated in S phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What does telomerase do?

A

recognise the tip of an existing telomere repeat sequence and the catalytic subunit elongates it in the 5’ to 3’ direction with strings of TTAGGG repeats in the absence of a complementary DNA strand, using its RNA component as the template to synthesis a new copy of the repeat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why do somatic cells experience telomere shortening with each cell division?

A

they do not express telomerase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are uncapped chromosomes sensitive to?

A

degradation and fusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How are terminal sequences arranged in telomeres?

A

a linear pattern

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What do shelterin complexes do?

A

protect the ends of chromosomes and maintain and regulate telomere length

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What does the end replication problem hypothesise?

A

the ends of linear DNA cannot be replicated completely during lagging strand DNA synthesis; the removal of the RNA primer creates a gap and the strand becomes shorter with every successive round of DNA replication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Give examples of cells that proliferate and express telomerase

A
  • stem cells
  • cancer cells
  • intestinal epithelial cells
  • bone marrow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does the telomere hypothesis of ageing propose?

A

sufficient telomere loss on one or more chromosomes in normal somatic cells triggers cell senescence, whereas reactivation of the enzyme is necessary for cell immortalisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the evidence for the telomere hypothesis of ageing?

A
  • progressive telomere shortening in normal cells from young individuals frown in culture
  • shorter telomeres in colonic mucosa and blood than in foetal tissue and sperm
  • telomeres are shorter in most somatic tissues from older individuals
  • cell strains with shorter telomeres underwent fewer divisions in vitro
  • progeria children have short telomeres compared to age-match controls
17
Q

What happens when there is abundant telomerase?

A

addition and shorting stay balances and cells keep dividing which can lead to most human cancers

18
Q

What happens when there is insufficient telomerase?

A

cell division stops after a delay and senescence kicks in as well as cell malfunctions and genomic instability

19
Q

What happened in telomerase KO mice?

A

they survived for 6 generations because mice have longer telomeres to begin with

20
Q

How can longevity be calculated?

A

if the initial length of the telomere is known

21
Q

Why were chromosome fusions observed in later generations of telomerase KO mice?

A

due to the absence of telomeres at one end of the chromosome (Robertsonian-like configuration)

22
Q

What was observed in telomerase KO mice?

A
  • age-dependent telomerase shortening and associated chromosomal instability
  • shortened lifespan and specific skin defects
  • decreased body weight and reduced capacity to respond to stress
  • increased spontaneous malignancies
23
Q

Give examples of genetic disorders related to telomeres

A
  • Hutchison-Gilford progeria
  • Ataxia telangiectasia
  • Werner’s syndrome
  • Down’s syndrome
24
Q

What proportion of fibroblasts can bypass senescence by telomerase?

A

1 in 10 million

25
Q

What is the M1/M2 model of senescence?

A

the continuous loss of telomeres induces M1 senescence, which causes cell division arrest, followed by an M2 crisis that involves further extensive telomere attrition in the absence of cell cycle checkpoints

26
Q

What was observed when telomerase was introduced into normal human cells to study the extension of lifespan?

A
  • elongated telomeres
  • vigorous cell divisions in culture
  • reduced staining for β-galactosidase (senescence biomarker)
  • normal karyotype
  • 20 periods more than normal lifespan
  • causal relationship between telomere shortening and cellular senescence
27
Q

What is a karyotype?

A

an individual’s complete set of chromosomes

28
Q

What are potential uses of introduced telomerase into normal cells?

A
  • bone marrow transplants (haematopoietic stem cells)
  • skin grafts for burn patients (keratinocyte stem cells)
  • muscular dystrophy (satellite cells)
  • general immunity (AIDS)
  • ageing skin (fibroblasts)
  • cardiovascular disease (endothelial cells)
  • macular degeneration (retinal cells)
  • basic research and production of human products
29
Q

What was observed in the study that explored the immortalisation of lung fibroblasts by telomerase?

A
  • growth in low oxygen and antioxidants extended the life span of both foetal and adult fibroblasts
  • hTERT immortalises adult lung fibroblasts at ambient oxygen but not foetal lung fibroblasts
  • foetal lung fibroblasts could not be immortalised in ambient oxygen in spite of telomere elongation by telomeres – more widespread oxidative damage
  • both end replication and oxidative damage events contribute to telomere shortening in lung fibroblasts in vitro
30
Q

What does oxidative stress do?

A
  • produce free radicals which cause DNA damage
  • accelerate telomere shortening
31
Q

What are the benefits of longer telomeres at a genetic level?

A

lower risk of CAD and AD

32
Q

What are the risks of longer telomeres at a genetic level?

A

cancer

33
Q

What are the benefits of longer telomeres at a non-genetic level?

A

lower risk of incident diseases and mortality

34
Q

What does telomere dysfunction drive?

A

mitochondrial defects and tissue inflammation

35
Q

What is telomere dysfunction related to?

A

the cellular ageing markers

36
Q

What lifestyle changes can lengthen telomeres?

A
  • diet (increase in veg-based protein, fruits and veg and decrease in carbs)
  • exercise
  • stress management
  • increased social support
37
Q

What happens to telomeres in bats?

A

they do not shorten with age

Functional Ageing (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions