BIOL253 L6

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  • Created by: Katherine
  • Created on: 07-04-17 16:42
What is DNA damage?
It is a change to the regular chemical structure of the DNA double helix.
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Give examples of DNA damage:
Break in phosphodiester backbone, loss of a base, alteration to the structure of a base or mismatched base pairs.
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What causes a mutation?
DNA damage leads to mutation if damaged DNA is replicated.
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What is a mutation?
It is defined as a permanent heritable change in the sequence of an organism's genome
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What is a point mutation?
Involve alteration, insertion or deletion of one or a few bases at a time
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What are chromosome mutations?
(Anything where a larger piece of DNA is effected) E.g. Deletions, inversions, duplication, translocations.
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What do you call a change in chromosome number?
Aneuploidy
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What is a transposon insertion?
Mobile bits of DNA moving around within the genome
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How to we classify mutations?
Base pair substitution mutations
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What is a transition mutation?
Where a purine in one strand, is repalced by a different purine in the same strand, A pyrimidine in a different strand, is replaced by another pyrimidine in the strand.
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What is a transversion mutation
A pyrimidine changes to a purine
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Which have a greater effect, transversions or transitions?
Transversions.
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What is a misense mutation?
A mutation changes the encoded amino acid to a different amino acid.
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What is a nonsense mutation?
A mutation changes the encoded amino acid to code for a stop codon.
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What is a neutral mutation?
A change from an amino acid to another amino acid with similar chemical properties; e.g a change from AT to GC transition mutation changes the codon from lysine to arginine. May not have any effect on protein function
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What is special about neutral mutation?
The changed encoded amino acid will have similar properties.
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What is a silent mutation?
A change in codon such that the same amino acid is specified.
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What is a frameshift mutation?
Addition or deletion of one or a few base pairs leads to a change in reading frame. E.g. the insertion of a GC base pair scrambles the message after glutamine.
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What are forward mutations?
Mutations that change the wild type active form of protein to a mutant defective form?
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What are reverse mutations?
A mutation that converts a protein back to an active form.
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How are reversion mutations further classified?
True, partial
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What is a true reversion?
It restores sequene to code for the wild type amino acid in affected protein (back to the original codon).
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What is a partial reversion?
Changes sequence at site of original mutation to some other amino acid that fully or partially restores proteinn function.
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What is a suppressor mutation?
It changes sequence at a different location from original mutation in way that compensates for original mutation - intragenic, intergenic suppressors.
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What does intragenic mean?
Within the same gene
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What does intergenic mean?
A mutation in one polypeptide of a complex can be compensated for by a different polypeptide in a complex.
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Most mutations are..
Spontaneous
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How do you quantify mutations?
Germline nucleotide s
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What does random mean?
Changes that happen by chace, sometimes happen to be adaptive.
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What does adaptive mean?
Organisms 'direct' mutations to adapt to a particular environment.
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How do spontaneous mutations arise?
As a result of replication containing premutagenic damage, caused by DNA replication errors or Endogenous DNA damage.
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Give examples of DNA replication errors:
Nucleotide or template tautomerism causing mismatches
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Give examples of Endogenous DNA damage:
Base deamination, base loss, base modification as a result of exposure to metabolic products
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there are mechanisms to enusre the fidelity of DNA synthesis, how often do mutations arise that need to be fixed?
Base pairing (10^-1-10^-2), DNA polymerase (10^-5-10-^6), Accessory proteins (10^-7), Post replication mismatch repair (10^-9-10^-10)
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What is the overall rate of misincorporated nucleotides not repaired?
1 In 10^-9 - 10^-10
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Why is it important that DNA replication is faithful?
Mismatches arising from replication errors can become fixed (made permanent) as mutations following a further round of DNA replication. All subsequent generations will inherit this mutations.
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How is DNA replication errors a source of mutations?
Mismatches can be introduced as a result of base tautomerisation.
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What is base tautomerisation?
Bases adopt a rare tautomeric form, either in the template strand, or in the incoming nucelotide within the DNA polymerase active site.
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What do Tautomers form?
They form non-Watson Crick base pairs, so incorrect nucelotide incorporated, resulting in mismatch.
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Why is the endogenous damage, hydrolysis (depurination) bad?
Depurination of G leaves Apurinic site (AP site) with no base attached to deoxyribose. It is a premutagenic lesion.
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What is depurination
Hydrolysis of the glycosidic bond of the base and the sugar, resulting in relase of the base and a depurinated sugar.
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AP sites result in
Random base substitution or base skipping during replication. This leads to substitution or deletion.
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A further round of replication of damaged DNA results in
A mutation
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Do you get more depurination or more depyrimidination?
More depurination.
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The second thing that hydrolysis does is..
Deamination
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What is deamination
Amino group is removed.
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What happens if cytocine is denimated?
Results in uracil - uracil is not usually present in DNA
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What is the 3rd type of endogenous damage?
Alkylation
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What is alkylation?
Alkyl groups may be added to several different positions on bases by endogenous alkyl donors.
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What is the effect of Alkylation?
Base modification may affect base pairing properties of modified base
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What is the 4th type of endogenous damge?
Oxidative DNA damage - leads to spontaneous mutation
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How does Oxidative DNA damage occur?
Attack by ROS - 2300 bases damaged/cell/hr. Accounts for high mutation rate mitochondrial genomes.
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How can mutations be induced?
By exposure to mutagens
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What are chemical mutagens?
Base analogs, base modifying agents (including alkylating agents), intercalating agents
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What are physical mutagens?
Ionising radiation, ultraviolet radiation (UV)
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What is a classic base analog?
5-bromouracil (5BU)
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What does 5BU base pair with?
With Adenine (It behaves like thymine in its normal state)
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When 5BU tautomerises, what does it behave like?
It behaves like Cytosine and pairs with Guanine.
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What can you use base modifying agents for?
You can exaggerate things that usually go on - e.g. deanimation .
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What happens if you treat DNA with Nitrous acid?
Denimation
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What are the effects of removing an amino group?
From gauanine you get Xanthine which base pairs with cytosine (doesn't cause a mutation). Cytosine becaomes uracil. Adenine becomes hypoxanthine (results in a t to gc conditions - mutation)
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What is a base modifying agent?
Nitrous acid
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What are actions of modifying agents?
Deanimation, hydroxlates and methylates
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What is a modifying agent that hydroxylates?
Hydroxylamine
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How does Hydroxylamine work?
It hydrolyses Cytosine, removing an amine group and becoming hydroxylaminocytosine which base pairs with adenine
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What is a modifying agent that methylates?
Methylmethane (MMS)
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How does MMS work?
It is a potent alkylating agent. It methylates DNA in multiple positions. The methylation results in bases which can't be replicated or pre-mutagenic changes.
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How does MMS affect Guanine?
It changes it into O6 Methylguanine by adding a methyl group to the oxygen. This pairs with thymine.
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What type of damage is guanine susceotible to?
Alkylation, oxidation and deanimation
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Aside from modifying agents, what are other types of agents that induce mutations?
Intercalating agents induce frame shift mutations.
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What is an example of an intercalating agent?
Ethidium bromide
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What do intercalating agents do?
They have flat, planar structures that insert in the minor groove of the helix, resulting in partial unwinding. This leads to insertions and deletions on replication.
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What is a chemical agent in nature?
Benzopyrine.
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Other cards in this set

Card 2

Front

Give examples of DNA damage:

Back

Break in phosphodiester backbone, loss of a base, alteration to the structure of a base or mismatched base pairs.

Card 3

Front

What causes a mutation?

Back

Preview of the front of card 3

Card 4

Front

What is a mutation?

Back

Preview of the front of card 4

Card 5

Front

What is a point mutation?

Back

Preview of the front of card 5
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