CK L2 DNA Repair

Question 1

what is spontaneous deamination

Answer 1

the removal of an amino group from a molecule

Question 2

DNA Replication Stress

Answer 2

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

Question 3

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

Answer 3

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

Question 4

how can DNA replication stress occur?

Answer 4

if there is any machinery defects

Question 5

why can lots of errors cause DNA replication stress?

Answer 5

because it causes delays which in turn causes stress

Question 6

Types of DNA replication stress

Answer 6

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

Question 7

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

Answer 7

Repetitive DNA can lead to fork slippage

Question 8

Fork slippage leads to…?

Answer 8

trinucleotide

Question 9

trinucleotide repeat disorders

Answer 9

Huntingtons disease

Question 10

trinucleotide repeat disorders- some info on Huntingtons disease

Answer 10

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

Question 11

3 different outcomes of DNA damage response

Answer 11

> Senescence
Proliferation
Apoptosis

Question 12

Senescence is…?

Answer 12

permanent cell cycle arrest

Question 13

Apoptosis

Answer 13

Cell death

Question 14

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

Answer 14

> Senescence

> Apoptosis

Question 15

Proliferation…?

Answer 15

DNA repair

Question 16

what do cell cycle checkpoints do?

Answer 16

slow dow the cell cycle to allows for DNA repair

Question 17

the 4 steps in base excision repair

Answer 17

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

Question 18

what is a dimer

Answer 18

two identical subunits

Question 19

4 steps of Nucleotide excision repair

Answer 19

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

Question 20

4 steps of mismatch repair

Answer 20

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

Question 21

info on single strand breaks

Answer 21

> 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

Question 22

info in double strand breaks

Answer 22

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

Question 23

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

Answer 23

1) non-homologous end joining

2) homologous directed repair