DNA damage and repair

Question 1

What are human progeria syndromes?

Answer 1

Mutations lead to increased DNA damage
and/or failure to repair damage this then leads to premature ageing.

Question 2

How much DNA damage is present in each cell?

Answer 2

19,200

Question 3

How much DNA damage is there in the whole body?

Answer 3

710,000

Question 4

What are the sources of DNA damage?

Answer 4

Metabolism
UV light
Ionising radiation
DNA synthesis
Environmental mutagens

Question 5

What are ROS?

Answer 5

Reactive oxygen species

Question 6

Where do the reactive oxygen species come from?

Answer 6

Produced by every cell during metabolism in the mitochondria.

Question 7

What is the problem with 8-oxodG being in the body??

Answer 7

Causes pairing so bad DNA replication.

Question 8

How does UV lead to DNA damage?

Answer 8

Produces pyrimidine dimers in exposed tissue, these replicate single strand breaks which cause double strand breaks which are toxic.

Question 9

How does ionising radiation cause DNA damage?

Answer 9

Directly causes double-strand breaks which is the most toxic damage?

Question 10

What is a manmade ionising radiation?

Answer 10

Cancer treatment

Question 11

What wave range is UV light?

Answer 11

300nm

Question 12

Where does ionising radiation come from?

Answer 12

Radon
Cosmic rats
Radionucleotides

Question 13

How does DNA synthesis lead to DNA damage?

Answer 13

It is highly error-prone and DNA strand breaks occur.

Question 14

How many mistakes occur per replicated genome?

Answer 14

600

Question 15

What are environmental mutagens?

Answer 15

Food
Water
Air-borne
Smoking
Industrial

Question 16

How do cells cope with DNA damage?

Answer 16

DNA repair
They prevent the replication of damaged DNA, apoptosis kills damaged cells.

Question 17

What is MGMT?

Answer 17

O-6-methylguanine-DNA which is a DNA damage repair protein.

Question 18

Why isn’t MGMT an enzyme?

Answer 18

It can only function once.

Question 19

What is the direct role of MGMT?

Answer 19

Repairs methylation damage.

Question 20

What does global genome NER mean?

Answer 20

Involving the whole genome.

Question 21

What does T-coupled NER mean?

Answer 21

Involving the transcription complex part of the genome.

Question 22

What is NER?

Answer 22

Nucleotide excision repair

Question 23

What is nucleotide excision repair?

Answer 23

The primary mechanism for repair of UV induced
damage (XP).

Question 24

What is the difference between the global NER and t-coupled NER pathways?

Answer 24

Proteins which recognise damage.

Question 25

Which proteins recognise damage during t-coupled NER pathways?

Answer 25

CSA and CSB.

Question 26

Which proteins recognise damage during global NER pathways?

Answer 26

XB/C

Question 27

What is C syndrome?

Answer 27

Damage to CSA/B proteins which recognise the damage in t-coupled NER.

Question 28

What does C syndrome lead to?

Answer 28

TF2H complex abnormalities (transcription factors).

Question 29

What is Xeroderma pigmentosum?

Answer 29

Leads to XB mutations.

Question 30

What is Base excision repair?

Answer 30

The main mechanism for repair of oxidative damage. (Also alkylation, deamination, depurination/depyrimidination)

Question 31

What kinds of base excision repair exists?

Answer 31

Short and long patch.

Question 32

When is base excision repair used?

Answer 32

During single base damage.

Question 33

What is damage recognised by during base excision repair?

Answer 33

DNA glycosylase (OOG1).

Question 34

How was it proved that DNA glycosylase is used for recognition in base excision repair?

Answer 34

Using knockout mice.

Question 35

What is mismatch repair?

Answer 35

The primary mechanism for recognition of DNA mismatches arising during DNA replication.

Question 36

What kinds of mismatch repair occurs during DNA replication?

Answer 36

– Single base mismatches – Small insertion/deletions

Question 37

Why is mismatch repair important during cancer?

Answer 37

Recognises chemically-induced DNA damage, including important chemo-therapeutics.

Question 38

What is the risk with mutations to the mismatch repair pathway?

Answer 38

Mutations in this pathway are associated with familial colon cancer

Question 39

Why are double strand breaks the most toxic double-strand lesions?

Answer 39

Can lead to chromosome aberrations.

Question 40

What are the 2 different mechanisms of double-strand break repair?

Answer 40

– Non-homologous end joining. – Homologous recombination.

Question 41

What is the problem with non-homologous end joining?

Answer 41

It is highly error-prone, if ends are broken in the same place deletion occurs (however this prevents cancer).

Question 42

What is the positive of homologous recombination?

Answer 42

It is error free.

Question 43

When does homologous recombination ocuur?

Answer 43

Late S/G2.

Question 44

What is the most common solution to double stranded breaks?

Answer 44

Apoptosis.