Module 8 Lecture 1: Causes of DNA Mutation

Question 1

mutation

Answer 1

an alteration in the nucleotide sequence of a DNA molecule

Question 2

what are the two ways in which mutations can occur

Answer 2

1. errors in DNA replication- spontaneous mutations
2. mutagens- chemical or environmental agents that causes changes in DNA molecules

Question 3

what sequences are polymerases most likely to make mistakes with

Answer 3

repeated sequences

Question 4

what mistake is made by polymerases when reading repeating sequences

Answer 4

strand-slippage

Question 5

outline strand slippage

Answer 5

during polymerization, a newly synthesised strand is looped and a new nucleotide is added resulting in an extra nucleotide being put in
or
synthesis of new strand causes looping of the template strand meaning synthesis misses one strand causing one nucleotide to be deleted

Question 6

what does strand slippage result in?

Answer 6

a shift in the reading frame causing a new protein synthesis or an early stop codon

Question 7

tautomers

Answer 7

isomers with slightly different chemical structures

Question 8

base tautomerism

Answer 8

DNA polymerase is tricked as bases have different chemical forms
-bases have the potential to switch between different isomers causing a switch from one form to another
-the other form will have different base pairing functions causing the polymerase to read it wrong (can’t recognise the change)

Question 9

what are the normal bases called

Answer 9

amino-adenine (base pairs with T)
keto-thymine (base pairs with A)
keto-guanine (base pairs with C)
amino-cytosine (base pairs with G)

Question 10

what are the less common tautomer of the normal bases

Answer 10

imino-adenine (base pairs with C)
enol-thymine (base pairs with G)
enol-guanine (base pairs with T)
imino-cytosine (base pairs with G)

Question 11

base analogs

Answer 11

Chemicals that look like bases but aren’t bases; may be incorporated into DNA (by polymerase) during replication

Question 12

mutagens-direct structural change

Answer 12

Something from outside physically affects dna e.g uv, radiation or heat
-comes into DNA and directly affects it

Question 13

two ways in which mutagens can cause mutations

Answer 13

base analogs and direct structural change

Question 14

what is an example of an important base analog ans what is it an analog of

Answer 14

5-bromouracil (5bU)- occurs in the env not naturally in cells
analog of thymine (looks similar to thymine therefore maybe be added by polymerase during replication)

Question 15

when will the mutagen 5bU not haven an affect on DNA

Answer 15

if 5bU is in the form keto-5bU as keto-5bU base pairs with adenine
-it may be incorporated into DNA instead of T during replication

Question 16

what is the problem with 5bU

Answer 16

it commonly shifts to the enol-5bU tautomer which pairs with G not A not the keto form

Question 17

deaminating agents

Answer 17

change the structures of some nucleotides e.g nitrous acid and sodium bisulphite

Question 18

deamination

Answer 18

removal of amine groups

Question 19

why are amine groups important in bases

Answer 19

allows base pairs to form within DNA therefore removal will affect the base pairings of the DNA

Question 20

what does deamination adenine give and what is the effect

Answer 20

hypoxanthine
hypoxanthine pairs with C not T

Question 21

summary of the effects of deaminating agents

Answer 21

Deamination of cytosine gives uracil, pairs with A not G
Deamination of adenine gives hypoxanthine, pairs with C not T
Deamination of guanine gives xanthine, blocks DNA replication

Question 22

what is the effect of deamination of guanine

Answer 22

fatal

Question 23

alkylating agents

Answer 23

add alkyl groups to nucleotides

Question 24

example of an alkylating agent and effect

Answer 24

ethyl methane sulphonate (EMS) causes a transition mutation
-adding an alykl group to guanine no longer produces GC pairing it instead produces AT pairing

Question 25

intercalating agents

Answer 25

-insert between base pairs
-causes insertion mutations
-Brings apart the bases which means an extra nucleotide can be added by the polymerases causing insertion mutations

Question 26

example of an intercalating agent

Answer 26

ethidium bromide

Question 27

how does ethidium bromide insert between bases

Answer 27

flat molecule therefore inserts between bases on the side

Question 28

what is one of the worst mutations

Answer 28

UV

Question 29

effects of ultraviolet radiation

Answer 29

base dimerization and photoproducts

Question 30

why is DNA damage from UV the worst

Answer 30

as UV damage is not easy to repair unlike other DNA damage
-there isn’t a specific enzyme that can get rid of these products

Question 31

effect of heat on nucleotides

Answer 31

causes detachment of bass-gives rise to an AP site
-breaks the beta-N glycosidic bond causing the base to be cleaved off and the formation of an AP site

Question 32

AP site

Answer 32

AP= apurinic, apyrimidinic (depurination or depyrimidination)