Enabling replicative immortality hallmark of cancer Flashcards
What is the Hayflick limit?
Normal human cells have a limited capacity to divide. Usually 20-70 times.
This is caused senescence- cell stops dividing (ceased proliferation)
What are telomeres?
Telomeres are protective caps at the end of the chromosome.
This contains a hexametric nucleotide repeat- TTAGGG formed in a protein complex called Shelterin.
What is the purpose of telomeres?
Telomeres prevent the chromosomes from unravelling to prevent:
- Chromosome damage
- Chromosomes accidentally linking together during cell division
What happens to the telomeres when cells divide?
Each time the cell divides, the telomeres get slightly shorter until it leads to the ends of the chromosomes becoming frayed. This is the ‘Crisis point’
What is the crisis point?
This is when the telomeres have become so short that the ends of the chromosomes have become frayed. The cell will identify there are damage pits of DNA and will either:
- Go into senescence- long-term sleep
- Or undergo apoptosis
What is telomerase and its role?
Telomerase is a cellular reverse transcriptase enzyme
- It’s role is to add the DNA sequences (TTAGGG) onto the ends of the telomeres to prevent the shortening of the telomeres
What do 85-90% of all malignant tumours express?
TELOMERASE- this means that the telomeres are constantly kept at a longer length so the crisis point is never reached.
- The tumour cells bypass this crisis point by upregulating the telomerase enzyme and so can avoid the cell-cycle checkpoint genes= immortalised
What is the most common mutation in cancer?
Telomerase promoter mutations- common point mutation (a single base is changed, added or deleted)
Are there any anti-telomerase therapies available yet?
No none have been approved but this is an important therapeutic target in cancer therapies
