Topic 10: DNA damage response

Question 1

what does the DNA damage response include

Answer 1

the cellular pathways that sense, signal and repair DNA damage

Question 2

what are two types of damage

Answer 2

DNA damage and replication stress

Question 3

what is a brief overview of DNA damage response

Answer 3

DNA damage or replication stress -> sensors -> transducers -> effectors -> cell cycle stops or apoptosis or transcription or DNA repair activated

Question 4

what are the 3 outcomes in the DNA damage response as a last resort

Answer 4

Senescence = permanent cell cycle arrest (not divide but function)
Apoptosis = cell death
Proliferation = after DNA repair and cell cycle control (maintain function as dividing - ideal)
to maintain function of DNA if damage level are too high or persist

Question 5

how is cell cycle altered to allow DNA damage to be repaired

Answer 5

cell cycle is slowed down

Question 6

what response would occur is base was incorrect

Answer 6

base-excision repair

Question 7

what response would occur is nucleotides were joined together and became very bulky

Answer 7

nucleotide-excision repair

Question 8

what response would occur if insertion or deletion of bases would occur

Answer 8

mismatch repair

Question 9

what response would occur if double strand broke

Answer 9

recombinational repair

Question 10

what are the difference between different repairs

Answer 10

base-excision, nucleotide-exision, mismatch - single stranded
recombinational - double stranded (worse)

Question 11

what happens in base excision repair

Answer 11

1. deamination converts a cytosine base into uracil
2. uracil is detected and removed
3. the nucleotide it was a part of is also removed, leaving a hole in DNA backbone
4. the hole is filled with DNA polymerase and the gap is sealed by a ligase

Question 12

what happens in nucleotide excision repair

Answer 12

1. UV radiation produces a thymine dimer
2. the dimer is detected and surrounding DNA is opened to form a bubble
3. enzymes cut the damaged region out of the bubble
4. a DNA polymerase replaces the cut out DNA and a ligase seals the backbone
   * lots of proteins involved

Question 13

what happens in mismatch repair

Answer 13

1. a mismatch is detected in new strand
2. the new strand is taken out and the mispaired nucleotides and its neighbours are removed by exonuclease activity
3. the missing patch is replaced with the correct nucleotides, catalysed by DNA polymerase
4. a DNA ligase seals the gap in the DNA backbone

Question 14

what are the key features of single strand repair

Answer 14

simple
many different mechanisms
integrity of DNA molecule remains
the damage is removed from one strand only
homology of other strand is used as repair
not error free but not likely there will be error

Question 15

what happens in recombinational repair

Answer 15

two types: non-homologous end joining - cut of double strand and results in mutation when put together
homologous directed - broken DNA molecule uses DNA molecule of homologous pair as template to make perfect repair

Question 16

what are the key features of double strand repair

Answer 16

complex
integrity of DNA molecule is lost when cut two strands
more likely to be error prone
use of homology may be possible

Question 17

in what stages of cell cycle does non-homologous end joining increases

Answer 17

G1, S, G2

Question 18

in what stages of cell cycle does homologous directed repair increase

Answer 18

S phase, G2

Question 19

in what stage of cell cycle does homologous directed repair decrease

Answer 19

M, G1

Question 20

in what stages of cell cycle does non-homologous end joining decrease

Answer 20

M

Question 21

what occurs in non homologous end joining

Answer 21

1. the broken ends are recognised and protected
2. a complex formed and damaged ends removed
3. broken ends ligated
   ERROR PRONE

Question 22

what occurs in homology directed repair

Answer 22

double stranded break in one chromosome in homologous pair
the intact strand forms a bubble
resection of strand causes overhang which invades the other DNA helix
the overhang uses intact dna molecule to make new dna which extends
REPAIR IS PERFECT