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Biology - Genetics > Intracellularly - Telomeres > Flashcards

Intracellularly - Telomeres Flashcards

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AP® Biology flashcards Biology 101 flashcards
1
Q

Telomere

A

This protects chromosomal ends from erosion over cell divsions and against interchromosomal fusion

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2
Q

What happens when telomeres become too short?

A

Cell cycle arrest and apoptosis triggering

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3
Q

What are telomeres improtant for?

A

Genomic integrity.

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4
Q

What happens to telomeres every cell division?

A

They shorten, inducing instability of chromosomes

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5
Q

How do cancer cells achieve immortality?

A

Bypass shortening through telomerase production through TERT expression.

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6
Q

What causes increased hTERT expression in cancer cells?

A

Two mutations in the promoter region about 130BP upstream of TERT translation site.

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7
Q

What are techniques used to induce cell death of cancer cells?

A

Antisense oligonucleotides
Immunotherapy
G-Quadruplex Stabilisers
Small Molecule Inhibitors

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8
Q

Shelterin Complex

A

This regulates telomerase activity by binding telomeres and inducing t-loop formation.

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9
Q

T Loop

A

A cap of 300 BP ssDNA stabilising telomere, preventing ends from being recognised as break points by DNA repair machinery.

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10
Q

What sequence are telomeres rich in?

A

Tandem repeats of TTAGGG

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11
Q

How long is the teloemre?

A

About 10-15KB long.

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12
Q

What terminates the telomeres tandem repeats?

A

A 150-200 NT long overhang.

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13
Q

What is the function of the telomere overhang?

A

Forms T-Loop by folding back onto the 3’ strand, invading the TTAGGG region.

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14
Q

What are the components of the Shelterin Complex?

A

TRF1 and 2 heterodimer associated to POT/TPP1 heterodimer linked by TIN2.

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15
Q

TRF1

A

Controls replication of telomeric DNA

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16
Q

TRF2

A

Required for T-Loop formation and DDR supression and repression mediated by ATM preventing end-end chromosomsal fusion

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17
Q

POT1

A

Associates TPP1 and ss 3’ overhang and represses recruitment of RPA

18
Q

TIN2

A

Links the POT1/TPP1 heterodimer to the TRF1/2 heterodimer, maintaing structural integrity.

19
Q

TERRA(Telomeric Repeat ContainingRNA)

A

A long, non-coding RNA essential for integrity, functioning in heterochromatin reguloation, teloemrase regulation and DDR

20
Q

How much is TL reduced per cell division?

A

About 50-150BP

21
Q

Replicative Senescences

A

This is where nonmalignant cells stop divding after about 50 cell divsions.

22
Q

M2 Crisis

A

When telomeres are so short they cannot form protective structures to protect chromosome ends.

23
Q

How do cancer cells bypass M1?

A

Expression of reactivating telomerase expression OR teloemrase independet ALT mechanisms.

24
Q

ALT mechanisms

A

A mechanism of which cancer cells use to bypass telomeric degradation.

25
Q

How many cells in a pool of M1 undergo M2?

A

1 in 5 million.

26
Q

What are the components of telomerase holoenzyme?

A

TERT (telomerase reverse transcription)
hTERC (Human telomerase RNA component)
NHP, NOP10, Dyskerin and GAR1.

27
Q

What is the general assembly process of Telomerase?

A

Translocation of hTERT to the nucleus with assembly with hTR then telomerase recruitment.

28
Q

What do NHP, NOP1, dyskerin and GAR1 do?

A

Associate with small, nucleoalr RNA important in pseudouridylation

29
Q

Pseudouridylation

A

The process of conversion of uridine to pseudouridine within RNA.

30
Q

TCAB1

A

Binds hTR sequecne to direct holoenzyme to Cajal Bodies of the nucleolus.

31
Q

What is the process of Telomerases function?

A

Diassociates TPP1 and POT1 interactions of shelterin by DAT domains then synthesis from 3’ end.

32
Q

How does telomerase mediate TPP1 and POT1 diasscoation?

A

A DAT domain binds amino acid rich Tel patch of TPP1 and binds POT1 and TIN2.

33
Q

End Replication Problem

A

This proposes that linear DNA ends are not replicated completely during lagging strand DNA synthesis

34
Q

What happens to G-rich/C-rich strands in replication?

A

G-rich by leading strand synthesis and C-rich by lagging strand synthesis.

35
Q

Why is the lagging strand not completely replicated.

A

There is no room for okazaki fragment RNA primers to bind, resulting in an overhang and shortened telomere

36
Q

How does telomerase bypass End Replication Problem?

A

Increases leading strand to allow okazaki fragment RNA primer to be placed.

37
Q

What repair systems are DSB telomeres recognised by?

A

NHEJ
Homologous recombination repair

38
Q

What is the first step in NHEJ and HRR?

A

MRN complex recognises DSB, activating ATM

39
Q

What does ATM do after being activated by MRN?

A

Phosphorylates DNA repair proteins activating them

40
Q

What is the major DSB pathway?

A

NHEJ?

41
Q

When might HRR be activated?

A

If NHEJ does not repair quick enough, ATM activates other two pathways by generation of SS 3’ strand overhang.

42
Q

Why are cancer cells immortal?

A

Upregulation of catalytic subunit TERT of telomerase.

Biology - Genetics (14 decks)

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