7 - Telomeres and Telomerases Flashcards
What are telomeres?
highly repetative G-rich sequences containing a 3’ overhang at chromosome tips
What is the function of telomeres? Why?
to stabilize the ends of chromosomes | 3’OH = unprotected and susceptible to exonucleases and degradation
Once a cell continues to undergo cell division and the telomeres become short, what will happen to this cell?
cell undergoes crisis »_space;> induces apoptosis
What would be a reason why cells need to die?
they will accumulate more mutations and cause more problems
What is needed for DNA polymerase to jump onto the DNA?
RNA primer by primase
What is telomere shortening?
gap at the ends created post-replication due to removal of primer | every replication cycle = chromosomes shorten
What is the mitotic clock?
how cells measure time based on how many times they’ve gone through mitosis
What is the difference between crisis and senescence? What are these events due to?
crisis = cell can no longer divide, very short telomeres »_space;> leads to senescence = permanent G0 = last part of mitotic clock = will die at one point | due to very short telomere
How many cell types are in our bodies?
230
How many times do cells divide before they die?
depends on cell type | avg 20-70 times before senescence
What is Senescence-Associated Beta-Galactosidase?
biomarker associated with cellular aging
What is the relationship of beta-galactosidase with senescent cells?
as cells enter senescent, they release b-gal (beta-galactosidase)
Where does the “immortality” characteristic of tumor cells come from?
accessing and expressing telomerase to extend its telomeres
What is telomerase?
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
What are hTERT and hTR?
hTERT = human telomerase reverse transcriptase | hTR = human template for replication
Where are the 5 places that exhibit telomere elongation due to telomerase activity?
germ cells | stem cells | tumor cells | mouse (murine) cells | during embryogenesis
What is the role of telomerase in most normal cells?
low activity | used only for cap maintenance, not elongation
What is PinX1?
telomerase inhibitor = regulates telomerase activity | binds to reverse transcriptase portion
Is PinX1 pro or anti-tumor?
anti-tumor
How is senescence a dominant phenotype?
when immortal cell was fused with a mortal normal cell = created mortal hybrid
What are the 4 barriers to tumor progression?
tissue barriers | blood supply | senescence | crisis
What proteins are involved with senescence?
p53 and Rb
What keeps a tumor from migrating?
connective tissue
What does mutation of p53 allow the tumor to do?
allows uncontrolled cell division
What should one do if they want to know how dangerous a sarcoma is?
biopsy = look at telomerase activity and see if it has metastasized
What does telomerase activity in a sarcoma indicate?
cells have already immortalize
What is the TRAP assay?
telomeric repeat amplification protocol indicates presence of telomerase | patient tumor cell samples are lysed = use the telomerase »_space;> add very short artificial chromosome = if its elongated (seen in PCR) = telomerase present
When do WBCs turn on survival genes and telomerase?
when they are fighting a viral infection
What does a high level of hTERT in a patient indicate?
longer the telomeres will get
What does a high level of telomerase in a patient indicate?
the worse prognosis in the patient
What are the 2 parts (portions) of telomerase?
TERT (protein part) | RNA template (hTR)
What is the “break-fusion-bridge” cycle due to telomere cap loss?
loss of telomeres causes fusion between sister chromatids due to microhomology at telomere end (hexamer repeat)
What are chimeric chromosomes?
bridge from break-fusion-bridge cycle = break off and broken end is fused with an end piece of a different chromosome
What will occur if p53 is mutated in a cell whose telomeres shorten and uncap?
mutant cell divides but will die due to too much instability unless telomerase is activated
What is the issue with inhibiting telomerase as a treatment?
will affect stem cells
How do tumor cells elongate their telomeres other than with the help of telomerase?
performing a strand invasion next to any chromosome and use its telomere as a template
Why do mice always have telomerase on?
elongates their lifespan as they will age super quickly if they don’t have telomeres
With the development of any cancer drug, what is a question must you ask yourself?
Am I going to hit other cells or something else?
