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Flashcards in CK L2 DNA Repair Deck (23)
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1

what is spontaneous deamination

the removal of an amino group from a molecule

2

DNA Replication Stress

Inefficient replication that leads to replication fork slowing, stalling and/or breakage

3

why is it imortant that spontaneous mismatches get repaired straight away?

because it will have a knock on effect during replication where a single mismatch will effect lots once its has been replicated

4

how can DNA replication stress occur?

if there is any machinery defects

5

why can lots of errors cause DNA replication stress?

because it causes delays which in turn causes stress

6

Types of DNA replication stress

> Replication machinery defects
> Replication fork progression hindrance
> defects in response pathways

7

how can repetitive DNA slow down DNA machinery and cause DNA replication stress

Repetitive DNA can lead to fork slippage

8

Fork slippage leads to...?

trinucleotide

9

trinucleotide repeat disorders

Huntingtons disease

10

trinucleotide repeat disorders- some info on Huntingtons disease

> CAG repeats
> polylgutamine repeats
> normal protein function still unknown
Mutant protein aggregates in neurons
> progressive, late onset disease

11

3 different outcomes of DNA damage response

> Senescence
> Proliferation
> Apoptosis

12

Senescence is...?

permanent cell cycle arrest

13

Apoptosis

Cell death

14

if DNA damage levels too high or persist what are the two outcomes

> Senescence
> Apoptosis

15

Proliferation...?

DNA repair

16

what do cell cycle checkpoints do?

slow dow the cell cycle to allows for DNA repair

17

the 4 steps in base excision repair

1) deamination converts one base into another e.g C into U (this is the error)

2) U is detected and removed leaving base-less nucleotide

3) Base-less nucleotide is removed leaving small hole in DNA backbone

4) The hole is filled with the right base by a DNA polymerase and the gap is sealed by ligase

18

what is a dimer

two identical subunits

19

4 steps of Nucleotide excision repair

1) UV radiation produces a thymine dimer

2) once the dimer has been detected the surrounding DNA is opened to form a bubble

3) enzymes cut the damaged DNA region out of the bubble

4) a DNA polymerase replaces the excised (cut-out) DNA and a ligase seals the backbone

20

4 steps of mismatch repair

1) a mismatch is detected in newly synthesised DNA e.g G paired with T.

2) the new DNA strand is cut and the mispaired nucleotide and its neighbours are removed by exonuclease activity

3) the missing patch is replaced with correct nucleotides by a DNA polymerase

4) a DNA ligase seals the gap in the DNA backbone

21

info on single strand breaks

> relatively simple
> many diff mechanisms
> integrity of DNA molecule intact
> damage removed on one strand only
> homology of other strand used to repair
> not error-free but not error prone either

22

info in double strand breaks

> complex
> integrity of DNA molecule lost
> more likely to be error prone
> use of homology may be possible

23

what are the two ways of repairing a double strand break?

1) non-homologous end joining

2) homologous directed repair