Enabling replicative immortality Flashcards
name of the 2 strands for DNA replication?
leading and the lagging strand
what is the lagging strand made up of? what do they require to initiate synthesis
discrete fragments
each requiring a new RNA rimer to initiate synthesis
what happens to the DNA at the end of the chromosome? why?
cannot be replicated as there is no DNA beyond the end to which the next RNA primer can anneal
what is the ‘end replication problem’?
as there is no DNA beyond the end to which the next RNA primer can anneal, the end gap cannot be replicated
since one strand cannot copy its end, what is needed?
for the addition of an extended sequence of DNA at the end of the strand- telomere
what is telomeric DNA?
Short DNA sequence of SIX nucleotides
what is the telomeric DNA sequence?
TTAGGG
How many times is TTAGGG repeated?
depends on the number of divisions the cell has been through
what is the name of the enzyme which catalyses the addition of the extended DNA at the end of the chromosome?
telomerase
what does telomeric DNA at the end of the chromosome also prevent?
end to end fusion
chromosomal recombination
why can end to end fusion result in cancer?
as when this occurs, at the end of mitosis when the chromatids split, the separation can occur at random sites, meaning there will be defective chromosomes= cancer
how many times can mammalian cells replicate?
a limited number of times
what acts as a molecular clock that monitors the replicative history of the cells?
the gradual shortening of telomeres
do telomere get shorter or longer with time?
shorter
what do the cells do when they detect very short telomeres
detects it as cell damage
growth arrest or initiation of apoptosis
what happens in malignant cells regarding the arrest when telomere get short? what is the usual cause of this?
they bypass the arrest- become immortalised by telomere extension
due to telomerase being constantly on
targeting telomere can be important in not only anticancer, but also..
anti ageing
in which cancers is telomerase over-expression seen in?
most advanced cancers
what can be introduced to telomerase positive cancer cells? effect of this?
an RNA which is complementary in sequence to the human telomerase RNA of the telomerase enzyme
can anneal forming an RNA RNA double helix and block the ability of hTR subunit to synthesise telomeric DNA
example of a telomerase inhibitor?
imetelstat
imetelstat MOA?
complementary to the template region of the telomerase RNA
competitive enzyme inhibitor that binds and blocks the active site of the enzyme.
