Lectures 5 and 6: Mechanisms of Mutation

Question 1

What is genetic variation?

Answer 1

The differences in the DNA sequence of individuals in a population

Question 2

What are mutations?

Answer 2

Random events that occur due to environmental factors or failure of repair

Question 3

Can mutations be repaired?

Answer 3

Yes

Question 4

Define Mutation:

Answer 4

A change in the DNA sequence that arises de novo in an individual or tissue

Question 5

Define Polymorphism:

Answer 5

A germline DNA sequence variation that can be stably inherited

Question 6

What are the external factors that cause mutations?

Answer 6

• Mutagens like radiation and chemicals which cause depurination, demethylation and deamination
• Presence of Base Analogues

Question 7

How do external factors cause mutations?

Answer 7

They can cause direct structural effects or act indirectly by causing cells to produce other chemicals that have an effect

Question 8

What are the internal factors that cause mutations?

Answer 8

• Replication errors

- Replication must be faithful otherwise accumulated deleterious mutations would be incompatible with life

Question 9

What are tautomers?

Answer 9

Isomers of a compound that exist in equilibrium

Question 10

The stable form of T and G is the ______ form, the unstable form is the ______ form.

Answer 10

Keto

Enol

Question 11

The stable form of A and C is the ______ form, the unstable form is the ______ form.

Answer 11

Amino

Imino

Question 12

Unstable tautomers can form _____________.

Answer 12

Unstable pairs (i.e A-C or T-G)

Question 13

What is a mutagen?

Answer 13

An agent that causes an increase in the rate of mutation by causing chemical changes to the bases

Question 14

Deamination can be induced by _______ or occur _______________.

Answer 14

HNO2 or occur spontaneously

Question 15

When cytosine is deaminated we get __________. When 5-methylcytosine is deaminated we get __________.

Answer 15

Uracil

Thymine

Question 16

What do alkylating agents do?

Answer 16

Donate their alkyl groups to other molecules, this can cause transitions, transversions, frameshifts and chromosome aberrations

Question 17

With respect to bases, what is a transition?

Answer 17

Change from one purine to another or from one pyrimidine to another

Question 18

With respect to bases, what is a transversion?

Answer 18

Change from a purine to a pyrimidine

Question 19

What is depurination?

Answer 19

The loss of a base caused by the hydrolysis of the N-glycosidic bond of a purine ring that binds to the sugar part of the nucleotide. The base is replaced at random

Question 20

What is a base analogue?

Answer 20

A compound with similar structure to the normal bases but causes an increase in the freq. of mutations

Question 21

What is 2-aminopurine?

Answer 21

An analogue of adenine that pairs with cytosine

Question 22

What is 5-bromouracil?

Answer 22

An analogue of thymine that pairs with guanine

Question 23

What are intercalating agents?

Answer 23

Thin plate-like hydrophobic molecules that insert themselves between adjacent bases, they are usually +’vely charged

Question 24

What does ionising radiation do?

Answer 24

Breaks covalent bonds between bases and causes chromosome aberrations

Question 25

How does UV light affect the DNA?

Answer 25

Causes purines and pyrimidines to form abnormal dimers .’. causes the DNA to bulge

Question 26

What is the error rate of DNA polymerase?

Answer 26

~1 in 10^4 - 10^5 initially, but is reduced to ~1 in 10^9 by repair mechanisms

Question 27

How do repair systems recognise a mistake?

Answer 27

Mismatched bases and loops cause bulges/bubbles in the DNA double helix that can then be recognised

Question 28

What are the 2 types of abnormalities that need to be fixed by the repair systems?

Answer 28

Base Mismatching

Damage to nucleotide structure (i.e. breaks in the chromosome or pyrimidine dimers)

Question 29

How are breaks in the DNA fixed?

Answer 29

DNA ligase

Question 30

How are chemically modified bases and mismatched pairs repaired?

Answer 30

Excision by base-specific DNA-glycosylases and then resynthesis

Question 31

How are pyrimidine dimers repaired?

Answer 31

Dimerization can be reversed by enzymes

Question 32

A relatively ______ amount of errors can be repaired by direct repair. i.e. ________________, _______________ and ________________.

Answer 32

Small

Breaks in the chromosomes, Alkyl group removal and some dimerisation

Question 33

What is the most common method of repair and how does it work?

Answer 33

Excision repair, damaged region is excised by endonucleases creating an apurinic or apyrimidinic site that is then resynthesized by DNA polymerase

Question 34

How is base-excision repair different to nucleotide-excision repair?

Answer 34

In BER the base is removed first, then the surrounding nucleotides
In NER the whole nucleotide is removed in one go

Question 35

How does a DNA glycosylase work?

Answer 35

It cuts between the base and sugar backbone

Question 36

___________ of microsatellites is more common than ___________. Which occurs may be based on the _______________.

Answer 36

Expansion
Contraction
Parent of Origin