telomeres and telomerase Flashcards
(26 cards)
What is the structure of a telomere?
Non-telomeric DNA → double-stranded telomeric DNA → single-stranded 3’ G-rich overhang (hundreds of bases).
What is a telomere?
A telomere is the natural structure at the end of a linear chromosome that allows it to behave differently from a DNA double-strand break.
What functions do telomeres serve?
Prevent chromosome end fusions, inhibit DNA damage checkpoint activation, and protect ends from exonucleases.
What is replicative senescence?
A state where cells stop dividing after a fixed number of divisions due to telomere shortening.
Why do telomeres shorten with replication?
Due to the end-replication problem where DNA polymerase cannot fully replicate the lagging strand ends.
What is the Hayflick limit?
The number of times a normal human cell population divides before entering senescence.
What is the shelterin complex?
A group of proteins that protect telomeres and regulate their length.
What does TRF1 do?
Binds double-stranded telomeric DNA, regulates length by inhibiting telomerase, and stabilises replication.
What does TRF2 do?
Binds telomeric DNA, promotes T-loop formation, and prevents DNA damage responses.
Why does the end replication problem occur?
DNA polymerase needs an RNA primer, and after removing the final primer, a gap remains at the 5’ end.
What are the consequences of telomere shortening?
Loss of protection, DNA damage signaling, replicative senescence, or apoptosis.
How does telomerase counteract telomere erosion?
hTERT adds TTAGGG repeats using hTR as a template.
What is ALT (Alternative Lengthening of Telomeres)?
A telomerase-independent mechanism where short telomeres use other telomeres as templates.
What happens when hTERT is expressed in fibroblasts?
Telomerase is activated, telomeres are elongated, and senescence is bypassed.
Which cells express telomerase?
Stem cells and ~85% of cancer cells; most somatic cells do not.
Why is telomerase repression important?
Acts as a tumour-suppressive mechanism by limiting cell lifespan.
What happens when telomeres become critically short?
They lose shelterin protection and activate ATM/ATR, stabilising p53 → p21 → G1/S arrest.
What is the result of telomere uncapping?
DNA damage response is activated, leading to permanent cell cycle arrest (senescence).
What causes telomere fusion?
Loss of TRF2 and telomere uncapping expose chromosome ends.
What are the effects of telomere fusion?
Breakage-fusion-bridge (BFB) cycles, chromosome bridges, and genomic instability.
What is Imetelstat (Geron)?
A telomerase inhibitor oligonucleotide targeting the TERC template.
What are G-quadruplex stabilisers?
Molecules like Telomestatin that lock telomeres, prevent lengthening, and promote uncapping.
What is OBP-301 (Telomelysin)?
A telomerase-specific oncolytic virus used in experimental therapies.
What is telomerase immunotherapy?
Uses TERT peptides to activate CD8+ T cells against cancer cells.
