HRR: DNA mutation

Question 1

Describe the difference between a transition and a transversion.

Answer 1

Transition: purine to purine or pyrimidine to pyrimidine base change; point mutation

Transversion: purine to pyrimidine or pyrimidine to purine base change; point mutation

Question 2

Specify 3 possible functional effects produced by a single base substitution.

Answer 2

missense, nonsense, and silent mutations

Question 3

define a missense mutation

Answer 3

changes the amino acid sequence

Question 4

define a nonsense mutation

Answer 4

forms a premature stop codon that can truncate the protein or promote its degradation

Question 5

define a silent mutation

Answer 5

no change in amino acid sequence

Question 6

Describe two types of mutations that can produce frameshifts.

Answer 6

Insertion: adding a base pair alters the reading frame

Deletion: adding a base pair alters the meeting frame

Question 7

What is an in-frame insertion or deletion?

Answer 7

Inserting or deleting in multiples of 3 base pairs

Question 8

Describe how tautomerization of bases causes transitions.

Answer 8

Certain tautomerizations can change the base, and therefore the bonds between bases, leading to substitution

Question 9

Describe why DNA methylation produces “hotspots” for mutations.

Answer 9

CbG islands are responsible for 30% of all single base changes

Question 10

What areas are “hotspots” for insertions

Answer 10

Single nucleotide run…T’s and A’s in particular

Question 11

How can alkylation impact DNA? Describe the three main ways

Answer 11

Substitutions: G can pair with T instead of C if it is alkylated

Depurination: loss of glycosidic bond generates an AP site (loss of purine or pyrimidine), which causes strand breaks. This can be dangerous but can be useful.

interstrand cross-links: N7 of G residues on opposing DNA strands link and distort the helix

Question 12

Describe benzopyrene and it’s relation to induced mutation

Answer 12

It is a polycyclic aromatic hydrocarbon is cigarette smoke that can form bulky adducts with G bases. This causes distortion in the DNA and can lead to cross linking and strand breaks.

Question 13

Describe psoralen and its relation to induced mutation

Answer 13

Have two reactive sites that can form adducts with bases

Question 14

Define the type of mutation that could result from the deamination of cytosine.

Answer 14

Spontaneous U in DNA if cytosine to uracil

Cytosine to thymine: cannot be recognized by DNA repair processes, meaning the mutation will likely pass through

Question 15

Differentiate between a spontaneous mutation and an induced mutation.

Answer 15

Induced mutations are due to environmental factors and things we are exposed to, while spontaneous mutations just occur

Question 16

Describe free radicals

Answer 16

They have a single unpaired electron; the concerning one is a reactive oxygen species known as a hydroxyl radical, as it can react with many things in our system to cause trouble

Question 17

Specify two types of DNA damage produced by the generation of free radicals.

Answer 17

Transversions: OH can generate 8 hydroxyguanine, which can cause transversions by pairing G to A instead of C

Deletions: OH can cause strand breaks, resulting in deletion of one or more base pairs when the breaks are repaired by non-homologous end joining

Question 18

Describe how direct repair of DNA strand breaks causes deletions.

Answer 18

When a strand break happens, rejoining the non-homologous ends can create a deletion.

Question 19

describe how exposure to UV light can cause mutations

Answer 19

Thymine dimers (photons of energy from UV light) can cause interstrand cross links (cyclobutene rings) that can distort the helix, cause strand breaks, impact DNA replication and transcription, etc.

Question 20

name spontaneous and induced causes of substitutions/ transitions and transversions

Answer 20

spontaneous: polymerase errors, tautomerization, deamination, depurination

induced: deamination by HNO2, alkylating agents, free radicals

Question 21

name spontaneous and induced causes of insertions

Answer 21

spontaneous: slipped mispairing, triplet repeats

induced: N/A

Question 22

name spontaneous and induced causes of strand breaks and deletions

Answer 22

spontaneous: depurination

induced: alkylating agents, free radicals, chemical adducts

Question 23

name spontaneous and induced causes of cross linking in DNA helix

Answer 23

spontaneous: N/A

induced: alkylating agents, chemical adducts, UV light

Question 24

substitution to what base cannot be recognized by DNA

Answer 24

thymine

Question 25

describe cross linking

Answer 25

alkylating agents form cross links between G residues on opposing strands, distorting the helix

Question 26

what is the consequence of 8-hydroxyguanine

Answer 26

G pairs to A