Enabling replicative immortality Flashcards

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1
Q

name of the 2 strands for DNA replication?

A

leading and the lagging strand

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2
Q

what is the lagging strand made up of? what do they require to initiate synthesis

A

discrete fragments

each requiring a new RNA rimer to initiate synthesis

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3
Q

what happens to the DNA at the end of the chromosome? why?

A

cannot be replicated as there is no DNA beyond the end to which the next RNA primer can anneal

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4
Q

what is the ‘end replication problem’?

A

as there is no DNA beyond the end to which the next RNA primer can anneal, the end gap cannot be replicated

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5
Q

since one strand cannot copy its end, what is needed?

A

for the addition of an extended sequence of DNA at the end of the strand- telomere

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6
Q

what is telomeric DNA?

A

Short DNA sequence of SIX nucleotides

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7
Q

what is the telomeric DNA sequence?

A

TTAGGG

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8
Q

How many times is TTAGGG repeated?

A

depends on the number of divisions the cell has been through

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9
Q

what is the name of the enzyme which catalyses the addition of the extended DNA at the end of the chromosome?

A

telomerase

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10
Q

what does telomeric DNA at the end of the chromosome also prevent?

A

end to end fusion

chromosomal recombination

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11
Q

why can end to end fusion result in cancer?

A

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

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12
Q

how many times can mammalian cells replicate?

A

a limited number of times

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13
Q

what acts as a molecular clock that monitors the replicative history of the cells?

A

the gradual shortening of telomeres

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14
Q

do telomere get shorter or longer with time?

A

shorter

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15
Q

what do the cells do when they detect very short telomeres

A

detects it as cell damage

growth arrest or initiation of apoptosis

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16
Q

what happens in malignant cells regarding the arrest when telomere get short? what is the usual cause of this?

A

they bypass the arrest- become immortalised by telomere extension
due to telomerase being constantly on

17
Q

targeting telomere can be important in not only anticancer, but also..

A

anti ageing

18
Q

in which cancers is telomerase over-expression seen in?

A

most advanced cancers

19
Q

what can be introduced to telomerase positive cancer cells? effect of this?

A

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

20
Q

example of a telomerase inhibitor?

A

imetelstat

21
Q

imetelstat MOA?

A

complementary to the template region of the telomerase RNA

competitive enzyme inhibitor that binds and blocks the active site of the enzyme.