DNA Damage and Repair

Question 1

What does damage of replication DNA cells cause?

Answer 1

Cancer

Question 2

What does damage of non replication DNA cause?

Answer 2

Ageing

Question 3

What are endogenous sources?

Answer 3

Reaction with molecules from inside the cell.
e.g. Deamination, Depurination

Question 4

What are exogenous sources?

Answer 4

Reactions with molecules from outside the cell.
e.g. Uv light damage, X rays, chemotherapy

Question 5

What is endogenous DNA damage?

Answer 5

Spontaneous DNA damage to a single strand. Effects nucleotide base.

Question 6

What is exogenous DNA damage?

Answer 6

DNA damage to double strand.

Question 7

What is deamination?

Answer 7

Removal of amino group.
Exogenous
Changes base, doesn’t delete base.
C-T transition
A-G transition

Question 8

What are purines and what are pyrimidines?

Answer 8

Purines: A G
Pyrimidines: T C

Question 9

What is depurination?

Answer 9

N glycosidic bond is cleaved. (Abasic site)
Deletes base.
In the new strand, the pair is deleted.
Endogenous

Question 10

What do frameshifts cause?

Answer 10

Missense mutation, missense proteins e.g. sickle cell anemia.

Question 11

What does UV light do?

Answer 11

Induces formation of pyrimidine.
Creates a double bond, which upsets the structure of DNA.
Can cause inter strand crosslinks and DNA-protein crosslink.

Question 12

What is an interstrand crosslink?

Answer 12

Bases cross over and join together.
Caused by Xray, radiation, topoisomerase II inhibitors.

Question 13

What is DNA-protein crosslink?

Answer 13

Protein binds to nucleotide base.
Caused by ROS, hydroxyurea.

Question 14

What are the 3 DNA repair pathways?

Answer 14

BER - base excision repair
NER- nucleotide excision repair
Translesion synthesis

Question 15

What is BER?

Answer 15

Base excision repair.
Repairs single base damage
Uracil glycosylase removes damaged base, replaces base.

Question 16

What is NER?

Answer 16

Nucleotide excision repair.
Repairs section of DNA
Removes section of DNA, DNA polymerase fills the gap and DNA ligase seals it.

Question 17

What is translesion synthesis?

Answer 17

Replicative DNA polymerase is removed.
Translesional DNA polymerase repairs damage.
However, lacks precision and can cause substitution or deletion.

Question 18

What are the two types of double strand break repair?

Answer 18

NHEJ (non homologous end joining)
HR (homologous repair)

Question 19

What is NHEJ?

Answer 19

The ends of the DNA where the break is are joined back together.
However, causes some deletion of the end of the DNA.
During G1 phase
Error prone

Question 20

What is HR?

Answer 20

Sister chromatid is used as a template to fix the break.
During S phase
Not error prone

Question 21

What are the 3 places where DNA damage is detected?

Answer 21

• G1
• Entry to S phase
• Entry to mitosis

Question 22

How is DNA detected and therefore the cell cycle stopped?

Answer 22

ATM/ATR kinase activated
Phosphorylation of p53
activated p21
Binds to regulatory region
Stops cell cycle

Question 23

What cells have a predisposition to breast cancer?

Answer 23

BRCA2 deficient cells.