Enabling Replicative Immortality W6

Question 1

How can telomer erosion cause cellular apoptosis and senescence

Answer 1

The hayflick limit

Cultured normal human cells have limited capacity to divide approx. 20-70 times

This cellular ageing is called senescence or ceased proliferation

Question 2

Telomers

Answer 2

are protective caps at the end of
repetitive DNA at the end of chromosomes and
consist of hexameric TTAGGG nucleotide
repeats and a protein complex (shelterin).

Telomeres keep chromosomes from unravelling
– preventing chromosome damaged or
accidentally linking to each other during cell
division. Like the plastic caps that prevent
fraying of shoelaces.

Question 3

Each time a cell divides …

Answer 3

the telomeres get
shorter and shorter. Eventually the ends of the
chromosomes become frayed, like a frayed
shoelace that’s missing its plastic cap.

Question 4

Crisis point

Answer 4

is triggered when the cell identifies
that there are damaged bits of DNA
• The result is either a kind of long-term sleep
known as senescence, or death.

Question 5

Telomerase

Answer 5

a cellular reverse transcriptase that adds DNA sequences (TTAGGG) onto telomeres to prevent shortening

Detected in 85-90% of all malignant tumours

Question 6

When telomerase becomes critically shortened

Answer 6

Triggers a DNA damage singal where cells can die (crisis) or become senescent

Tumour cells bypass this crisis by upregulating telomerase and avoiding cell cycle checkpoint genes