DNA Repair And Cell Cycle Flashcards

1
Q

Cell cycle- g1 phase

A

Cell content duplication

10-12 hours

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2
Q

S phase

A

DNA replication.

6-8 hours

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3
Q

G2 phase

A

3-4 hours

Double check and repair

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4
Q

M phase

A

Less than an hour

Mitosis

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5
Q

What are the exogenous sources of DNA damage

A
Ionising radiation 
UV
Alkylating got agents 
Mutagenic chemicals 
Anti-cancer drugs 
Free radicals
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6
Q

What is dna replication stress

A

Inefficient replication that leads to replication fork slowing, stalling and or breaks

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7
Q

How does DNA polymerase deal with misincorporation

A

DNA polymerase can sense it has replicated wrong therefore reverses so it can remove the wrong base and put the right one in- proofreading

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8
Q

What does fork slippage lead to

A

Trinucleotide expansion

Huntington’s, spinocerebellar ataxia, fragile X

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9
Q

What is senescence

A

Permanent cell cycle arrest

Wont divide anymore no function

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10
Q

Base excision repair

A

Used when there is the wrong base

  • deamination changes base
  • wrong base identified and removed leaving a base less nucleotide
  • base-less nucleotide removed leaving a small hole in the DNA backbone
  • hole is filled with the right base by DNA polymerase and gap is sealed by DNA ligase
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11
Q

Nucleotide excision repair

A
  • UV radiation produces a dimer
  • once the dimer is detected the surrounding DNA is opened to form a bubble
  • enzymes cut the damaged region out
  • a DNA polymerase replaced the excised DNA and ligase seals the backbone
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12
Q

Mismatch repair

A
  • mismatch is detected in newly synthesised DNA
  • new DNA strand is cut and the misread nucleotide and its neighbours are removed by exonuclease activity
  • missing patch is replaced with correct nucleotides by a DNA polymerase
  • a DNA ligase seals the gap in the DNA backbone
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13
Q

Non homologous end joining

A

Broken ends recognised and protected

Complex formed and damaged ends removed

Broken ends ligated

Error prone

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14
Q

What determines the type of DNA double strand break repair that occurs

A

The stage of the cell cycle that the cell is

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15
Q

Homologous directed repair

A

Firstly, the exposed ends of DNA are resected.

This mechanism utilises a homologous template – which essentially means an undamaged copy of the DNA involved in the double-strand break – e.g. a sister chromatid.

A Holliday Junction then forms between the broken DNA and the DNA template.

The Holliday Junction is then nicked complete the repair.

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16
Q

What is clonal expansion

A

Different clones in 1 tumour

17
Q

What negative effects can chemotherapy have on tumours

A

Clones of cells in a tumour have differential sensitivity to the chemo- the chemo may work on one cone but nit another so that one will continue to grow- shows why tumours shrink then grow back

Chemotherapy-induced mutagenesis- by trying to kill the clone you can mutate them even more making them more resistant to chemotherapy

18
Q

What are synthetic lethality strategies

A

If we know that a certain gene doesn’t work to keep the cell alive we can ensure that the only pathway the cell can take i that pathway which would kill the cancer cell by giving treatment that promotes that pathway

19
Q

What are some endogenous causes of mutation in DNA?

A

DNA replication errors

Free radicals