Mutation

Question 1

Suppressor mutation

Answer 1

genetic change that hids or suppresses the effect of another mutation

Question 2

Intragenic suppressor mutation

Answer 2

mutation suppresses a mutation in the same gene (restoration of reading frame)

Question 3

Intergenic suppressor mutation

Answer 3

mutation suppresses mutation in a separate gene (change the way that the mRNA is translated (encode a tRNA that adds an aa for a stop codon)

Question 4

Expanding trinucleotide repeats

Answer 4

Repeated sequence of 3 nucleotides in which the number of the trinucleotide increases (possibly caused by hairpins which cause the template to be replicated twice – can lead to fragile X syndrome)

Question 5

Bacterial gene mutation rates

Answer 5

10^-8 to 10^-10

Question 6

Eukaryotic gene mutation rates

Answer 6

10^-5 to 10^-6

Question 7

DNA virus mutation rates

Answer 7

10^-5 to 10^-6

Question 8

RNA virus mutation rates

Answer 8

10^-3 to 10^-5

Question 9

Causes of spontaneous replication errors (2)

Answer 9

1. Tautomeric shifts (allows for alternate base pairings); 2. Wobble (flexibility in helical structure allow alternate base pairings).

Question 10

Incorporated error

Answer 10

Mismatched base incorporated into a newly synthesized nucleotide chain

Question 11

Replication error

Answer 11

Original incorporated error leads to a permanent error after complementary strand is synthesized

Question 12

Strand slippage

Answer 12

Small insertions/deletions arise if one strand forms a small loop

Question 13

Unequal crossing over

Answer 13

Misaligned pairing of homologous chromosomes results in one DNA molecule with an insertion (and the other with a deletion)

Question 14

Causes of spontaneous chemical changes (2)

Answer 14

1. Depurination (loss of a purine base from a nt and an incorrect nt is added in a newly synthesized strand); 2. Deamination (loss of an amino group, deamination of C yields U which pairs with A).

Question 15

Types of chemically induced mutations (6)

Answer 15

1. Base analogs
2. Alkylating agent
3. Deamination
4. Hydroxylamine
5. Oxidative reactions
6. Intercalating agents

Question 16

Base analogs (definition and how they work)

Answer 16

chemicals with similar structures to nt bases. DNA polymerases cannot distinguish difference so add to newly synthesized DNA, which can then cause mismatching between bases. Ex: 5BU

Question 17

Alkylating agents (definition and how they work)

Answer 17

Add methyl and ethyl groups to bases. Akylation alters base pairing (e.g. adding an ethyl to G makes it pair with T).

Question 18

Deamination (definition and how it works)

Answer 18

Removes an amine group from a nt base. Results in mismatch base-pairing (e.g. deaminating C results in U which pairs with C)

Question 19

Hydroxylamine (definition and how it works)

Answer 19

Adds a hydroxyl group to cytosine. This increases the frequency of the rare C tautomer which pairs with A.

Question 20

Oxidative reactions (definition and how they work)

Answer 20

Reactive forms of oxygen (superoxide radicals, hydroxyl radicals) are produced and damage DNA. For example, oxidation converts G into 8-oxy-7,8-dihydrodeoxyguanine which mispairs with A.

Question 21

Intercalating agents (definition and how they work)

Answer 21

Agents that produce mutations by sandwiching themselves between adjacent bases in DNA. This distorts the 3D structure and causes single nt insertions and deletions upon replication.

Question 22

How does radiation cause mutations?

Answer 22

Ionizing radiation dislodges electrons from atoms and can alter the structure of bases and break phosphodiester bonds. UV light is absorbed by bases and results in the creation of pyrimidine dimers (T-T most frequent) which distort the configuration of DNA and block replication

Question 23

SOS system

Answer 23

System in bacteria that allows them to circumvent replication blocks produced by pyrimidine dimers (UV radiation). Allows bases to be inserted into a new DNA strand in the absence of bases on the template strand (results in numerous errors)

Question 24

DNA polymerase eta

Answer 24

Found in eukaryotic cells that bypasses pyrimidine dimers (UV radiation) and inserts AA opposite the dimer. Normally works since TT dimers are most common, but error-prone since CT dimers sometimes occur.

Question 25

Ames Test

Answer 25

Both cancer and mutations result from damaged DNA, so mutagens are likely carcinogens. Treat his- pops of Salmonella with a mutagen and see how many his+ revertants arise.

Question 26

What are the 4 common DNA repair systems?

Answer 26

1. Mismatch
2. Direct
3. Base excision
4. Nucletoide excision

Question 27

How does mismatch repair work?

Answer 27

Corrects incorrectly inserted nucleotides that escape detection by proofreading. Enzymes detect distortion in 3D structure, cut out the distorted section and fill the gap with new nucleotides. Identify template strand bc it is methylated.

Question 28

How does proofreading by DNA polymerase work?

Answer 28

Incorrect positioning of nt in the DNA pol active site stalls polymerization activity and induces the 3’–>5’ exonuclease activity of the DNA pol. This removes the incorrectly paired base and then inserts the correct one.

Question 29

How does direct repair work?

Answer 29

Changes altered nucleotides back into their original structure. For example, removes methyl group from an alkylated G to restore the original G.

Question 30

How does base-excision repair work?

Answer 30

Modified base is excised and then the entire nucleotide is replaced. After the altered base is removed, an enzyme called AP endonuclease cuts the phosphodiester bond and the deoxyribose sugar is removed. DNA pol then ads the new nt.

Question 31

How does nucleotide-excision repair work?

Answer 31

Removes bulky DNA lesions (e.g. pyrimidine dimers) that distort the double helix. Complex of enzymes scans DNA, looking for distortions in structure. When detected, enzymes separate strands, cleave sugar-phosphate backbone, peel away damaged strand, and fill gap via DNA pol and ligase.