7 - Telomeres and Telomerases

Question 1

What are telomeres?

Answer 1

highly repetative G-rich sequences containing a 3’ overhang at chromosome tips

Question 2

What is the function of telomeres? Why?

Answer 2

to stabilize the ends of chromosomes | 3’OH = unprotected and susceptible to exonucleases and degradation

Question 3

Once a cell continues to undergo cell division and the telomeres become short, what will happen to this cell?

Answer 3

cell undergoes crisis &raquo_space;> induces apoptosis

Question 4

What would be a reason why cells need to die?

Answer 4

they will accumulate more mutations and cause more problems

Question 5

What is needed for DNA polymerase to jump onto the DNA?

Answer 5

RNA primer by primase

Question 6

What is telomere shortening?

Answer 6

gap at the ends created post-replication due to removal of primer | every replication cycle = chromosomes shorten

Question 7

What is the mitotic clock?

Answer 7

how cells measure time based on how many times they’ve gone through mitosis

Question 8

What is the difference between crisis and senescence? What are these events due to?

Answer 8

crisis = cell can no longer divide, very short telomeres &raquo_space;> leads to senescence = permanent G0 = last part of mitotic clock = will die at one point | due to very short telomere

Question 9

How many cell types are in our bodies?

Answer 9

230

Question 10

How many times do cells divide before they die?

Answer 10

depends on cell type | avg 20-70 times before senescence

Question 11

What is Senescence-Associated Beta-Galactosidase?

Answer 11

biomarker associated with cellular aging

Question 12

What is the relationship of beta-galactosidase with senescent cells?

Answer 12

as cells enter senescent, they release b-gal (beta-galactosidase)

Question 13

Where does the “immortality” characteristic of tumor cells come from?

Answer 13

accessing and expressing telomerase to extend its telomeres

Question 14

What is telomerase?

Answer 14

telomere extending enzyme complex | holds a piece of RNA that H-bond to DNA hanging end = DNA pol jumps on it and fills in gap

Question 15

What are hTERT and hTR?

Answer 15

hTERT = human telomerase reverse transcriptase | hTR = human template for replication

Question 16

Where are the 5 places that exhibit telomere elongation due to telomerase activity?

Answer 16

germ cells | stem cells | tumor cells | mouse (murine) cells | during embryogenesis

Question 17

What is the role of telomerase in most normal cells?

Answer 17

low activity | used only for cap maintenance, not elongation

Question 18

What is PinX1?

Answer 18

telomerase inhibitor = regulates telomerase activity | binds to reverse transcriptase portion

Question 19

Is PinX1 pro or anti-tumor?

Answer 19

anti-tumor

Question 20

How is senescence a dominant phenotype?

Answer 20

when immortal cell was fused with a mortal normal cell = created mortal hybrid

Question 21

What are the 4 barriers to tumor progression?

Answer 21

tissue barriers | blood supply | senescence | crisis

Question 22

What proteins are involved with senescence?

Answer 22

p53 and Rb

Question 23

What keeps a tumor from migrating?

Answer 23

connective tissue

Question 24

What does mutation of p53 allow the tumor to do?

Answer 24

allows uncontrolled cell division

Question 25

What should one do if they want to know how dangerous a sarcoma is?

Answer 25

biopsy = look at telomerase activity and see if it has metastasized

Question 26

What does telomerase activity in a sarcoma indicate?

Answer 26

cells have already immortalize

Question 27

What is the TRAP assay?

Answer 27

telomeric repeat amplification protocol indicates presence of telomerase | patient tumor cell samples are lysed = use the telomerase >>> add very short artificial chromosome = if its elongated (seen in PCR) = telomerase present

Question 28

When do WBCs turn on survival genes and telomerase?

Answer 28

when they are fighting a viral infection

Question 29

What does a high level of hTERT in a patient indicate?

Answer 29

longer the telomeres will get

Question 30

What does a high level of telomerase in a patient indicate?

Answer 30

the worse prognosis in the patient

Question 31

What are the 2 parts (portions) of telomerase?

Answer 31

TERT (protein part) | RNA template (hTR)

Question 32

What is the "break-fusion-bridge" cycle due to telomere cap loss?

Answer 32

loss of telomeres causes fusion between sister chromatids due to microhomology at telomere end (hexamer repeat)

Question 33

What are chimeric chromosomes?

Answer 33

bridge from break-fusion-bridge cycle = break off and broken end is fused with an end piece of a different chromosome

Question 34

What will occur if p53 is mutated in a cell whose telomeres shorten and uncap?

Answer 34

mutant cell divides but will die due to too much instability unless telomerase is activated

Question 35

What is the issue with inhibiting telomerase as a treatment?

Answer 35

will affect stem cells

Question 36

How do tumor cells elongate their telomeres other than with the help of telomerase?

Answer 36

performing a strand invasion next to any chromosome and use its telomere as a template

Question 37

Why do mice always have telomerase on?

Answer 37

elongates their lifespan as they will age super quickly if they don't have telomeres

Question 38

With the development of any cancer drug, what is a question must you ask yourself?

Answer 38

Am I going to hit other cells or something else?