topic 6

Question 1

what is DNA damage

Answer 1

any modification of DNA that changes its coding properties or normal function in transcription or translation

Question 2

What are the 3 types of changes in DNA

Answer 2

1. gene mutation
2. recombination
3. transposable elements

Question 3

list the 7 types of chemical modifications for DNA

Answer 3

1. deamination
2. base loss by depurination /depyrimidination
3. oxidation – electron loss
4. alkylation
5. nitrous acid-induced DNA damage
6. energy-rich radiations cause inter-base, inter-strand c
   crosslinkings, and strand breaks
7. action of intercalating agents
8. other chemical mutagens, ie. base analogs

Question 4

result of point mutations

Answer 4

missense, nonsense mutations

Question 5

result of a frameshift mutation (new vs old strand)

Answer 5

• slippage of template → deletion
• slippage of new strand → addition

Question 6

what does the enol form of Thymine pair with?
how does this alter the DNA sequence?

Answer 6

keto form of Guanine
T:A → eT:G → C:G

Question 7

what does the enol form of Guanine pair with?
how does this impact the DNA sequence?

Answer 7

keto form of Thymine
G:C → eG:T → A:T

Question 8

what does the imino form of Adenine pair with?
how does this impact the DNA sequence?

Answer 8

amino form of Cytosine
A:T → iA:C → G:C

Question 9

what does the imino form of Cytosine pair with?
how does this impact the DNA sequence?

Answer 9

amino form of Adenine
C:G → iC:A → T:A

Question 10

What does base pairing of tautomeric forms of bases result in?

Answer 10

transitions or transversions

Question 11

What is a transition mutation?

Answer 11

exchange of purine-pyrimidine base pair for the other purine-pyrimidine base pair
- C::G -> T::A or T::A -> C::G

Question 12

What is a transversion mutation?

Answer 12

exchange of purine-pyrimidin
base pair with a pyrimidine-
purine base pair or vice versa
- C::G -> G::C or A::T

Question 13

What are the 2 steps of Substitution Point Mutation?

Answer 13

1. incorrect nucleotide incorporated by DNA pol during replication (mismatching)
2. mismatched based not repaired and is replicated (mutation)

Question 14

Cause of indels

Answer 14

aberrant DNA recombination or DNA polymerase slippage during replication

Question 15

how can the number of triplet repeats in fragile X locus be determined

Answer 15

length analysis of PCR products
- additional repeats creates longer segments

Question 16

how do alkylating agents chemically damage DNA?

Answer 16

electrophilic attack of the DNA backbone

Question 17

What type of reaction damages nucleotides and the phosphodiester backbone?

Answer 17

hydrolytic reactions with H2O

Question 18

Which bases can undergo deamination and what to they transform into?

Answer 18

– Cytosine → Uracil
– Adenine → Hypoxathine
– Guanine → Xanthine
– 5-Me-Cytosine → Thymine

THYMINE CANNOT BE DEAMINATED

Question 19

What do Hypoxathine and Xanthine base pair with?

Answer 19

Cytosine - can pair with, may also continue with their normal base

Question 20

What bond does hydrolytic reactions cleave?
What does this create?

Answer 20

• cleaves the glycosyl bond between the nitrogenous base and the deoxyribose
• creates an abasic (AP) site (aka apurinic or apyrimidinic site)

Question 21

what can depurination/ depyrimidination result in?

Answer 21

base loss or base-pair
transition

Question 22

Where might strand break and bass loss occur in deoxyribose?

Answer 22

Abasic Site

Question 23

What produces ROS? what is 1 function of ROS?

Answer 23

Reactive Oxygen Species (ROS)
- cellular metabolism, (cellular respiration in mitochondria,
detoxification in the liver, ionizing radiation)
- can function as DNA-damage reagents

Question 24

ROS reactions

Answer 24

oxidize:
thymine -> thymine glycol
guanine -> 8-oxo-guanine

Question 25

example of alkylating agent and where alkylation occurs

Answer 25

• ch3- (from cigarettes)
• mostly Ns and Os
• highly reactive sites: N3 of A and O6
  of G

Question 26

what type of damage does Nitrous Acid (HNO2 )- Induce?

Answer 26

deamination of
Guanine -> xanthine (bonds w/ C)
cytosine -> uracil (bonds with A)
adenine -> hypoxanthine (bonds w C)