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Genetics (MDSC 341) > Mutations, DNA Repair, and Recombination > Flashcards

Mutations, DNA Repair, and Recombination Flashcards

1
Q

What types of mutations are transitions and transversions?

A

Substitutions

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2
Q

What is a transition?

A

A base substitution where a purine changes to a purine or a pyrimidine changes for a pyrimidine.

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3
Q

What is a transversion?

A

A base substitution when a purine changes to a pyrimidine or vice versa.

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4
Q

What is a mutation?

A

A heritable change in DNA sequence which can either be somatic or germline.

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5
Q

Which one is always larger, the forward mutation rate or the reverse mutation rate?

A

The forward mutation rate (there are many paths to mutation but only a single path to reversion).

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6
Q

What is the fluctuation test?

A

A test to determine whether mutations for bacterial resistance arose in response to bacteriophages or were random (spontaneous mutations that occurred prior to exposure). Since surviving colonies had very diverse population sizes, fluctuation test determined mutations were spontaneous.

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7
Q

What are the five types of naturally occurring spontaneous DNA damage?

A

Depurination, deamination, x-ray double stranded breaks, UV light producing thymine dimers, and oxidation.

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8
Q

What is depurination?

A

When the hydrolysis of water causes a purine nucleotide to detach from the DNA strand, leaving the strand with an unspecified base. This causes a mutation 3/4 of the time (1/4 chance for correct base).

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9
Q

What is deamination?

A

When the amine group of a pyrimidine detaches, changing its identity. Most commonly, the deamination of cytosine to uracil (C to U) results in a DNA change of CG to AT.

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10
Q

How do x-rays cause double stranded breaks?

A

The X-rays break the DNA backbone, splitting it in half. These DNA fragments may be ligated back together improperly leading to a mutation.

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11
Q

What are thymine dimers?

A

UV light causes adjacent Ts to form thymine dimers that lead to substitutions when DNA is replicated.

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12
Q

How does oxidation result in DNA damage?

A

The oxidation of G to 8-oxodG by a an active oxygen species (free radical oxygen) causes 8-oxodG to pair with Adenine.

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13
Q

What is the result of strand slippage during DNA replication?

A

Small insertions or deletions.

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14
Q

If the daughter strand slips, does it result in an insertion or deletion?

A

Insertion.

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15
Q

If the parent strand slips, does it result in an insertion or deletion?

A

Deletion.

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16
Q

Does unequal crossing over result in a mutation?

A

Yes, one chromosome will have a duplicated section while the other will have a deleted section.

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17
Q

What are transposable elements?

A

A DNA sequence which, upon being replicated, can move to other locations in the genome, resulting in a mutation.

18
Q

What are tautomers?

A

Isomers of a compound that readily interconvert.

19
Q

How does tautomerization lead to mutation?

A

Rare base tautomers do not pair correctly. For example, the rare enol form of thymine pairs with guanine. The tautomers always pair purine to pyrimidine (like A with C, not A with G).

20
Q

How did Muller prove mutagens can be used to increase mutation?

A

Crossed bar eyed females to males who had been exposed to X-rays. Some of the offspring were bar eyed females, but all of these females carried a mutated X allele from the father. When these females were crossed to normal males, all male offspring were bar eyed, indicating a single mutated X allele as lethal (recessive lethal).

21
Q

What is a mutagen?

A

Any physical or chemical agent that raises the frequency of mutations above the spontaneous rate.

22
Q

What are base analogs?

A

Chemicals that are similar in structure to normal nitrogenous bases, but may have tautomeric forms that lead to improper base pairing.

23
Q

Are base analogs mutagens?

A

Yes, they increase the frequency of mutations above the spontaneous rate.

24
Q

What are hydroxylating agents?

A

These agents add a hydroxyl group to bases, causing them to pair improperly.

25
Q

What are alkylating agents?

A

These agents add an alkyl group (either a methyl or ethyl), causing improper base pairing.

26
Q

What are deaminating agents?

A

These agents remove amine groups, leading to improper base pairing.

27
Q

What are intercalators / intercalating agents?

A

Flat molecules that can sandwich themselves between successive base pairs, disrupting the machinery for replication and causing deletions or insertions of a base pair.

28
Q

What is the Ames test?

A

A test used to determine whether a compound is a mutagen. Histadine negative bacteria are grown with rat liver enzymes in media without histadine. One group is exposed to a potential mutagen, the other is not. If the bacteria begin to grow in the colony exposed to the potential mutagen, it is a mutagen.

29
Q

What is direct repair of damaged bases?

A

DNA repair that eliminates damage using chemical reversion that does not require a nucleotide template, breakage of the DNA backbone, or DNA replication.

30
Q

What are alkyltransferase enzymes?

A

Enzymes that remove mistakenly added akyl groups to bases, a form of direct repair.

31
Q

What is photolyase?

A

An enzyme not present in humans that recognizes thymine dimers and reverses the damage by splitting the chemical linkage between the thymines.

32
Q

What are the 5 steps in base excision repair?

A
  1. Glycosylase removes damaged base, leaving an apuryinic or apyrimidinic site (AP).
  2. Endonuclease creates a nick in the backbone at the AP site.
  3. Exonuclease removes nucleotides near the nick.
  4. DNA polymerase synthesizes new DNA to fill in the gap.
  5. DNA ligase seals the nick.
33
Q

What is the difference between nucleotide excision repair and base excision repair?

A

Nucleotide excision repair occurs in cells that lack the DNA glycosylase needed for base excision repair.

34
Q

How does nucleotide excision repair work?

A

Proteins will nick a stretch of DNA at both ends, causing the fragment to be released from the DNA. DNA polymerase and ligase fill in and seal the gap.

35
Q

How does DNA polymerase proofread?

A

As DNA polymerase synthesizes new strands of DNA, if it mistakenly adds an incorrect nucleotide at the 3’ end, exonuclease activity will remove that nucleotide, giving DNA polymerase another chance to add the correct one.

36
Q

How does mistmatch repair work in prokaryotes?

A

After DNA replication, proteins recognize mistmatched bases due to the kink in DNA they create. Using the methylated GATC sequences to identify the parent strand, another protein nicks the daughter strand before an exonuclease removes all nucleotides from the nick to a location just beyond the mismatch. DNA polymerase and ligase then resynthesize and seal the DNA. Enzymes then methylate GATC sequences of the daughter strand.

37
Q

What are two mechanisms of double-stranded DNA repair?

A

Non-homologous end joining, and homologous end joining.

38
Q

What is non-homologous end joining?

A

Following a double strand break, proteins bind to both sides of the breakage, bridging the two ends and allowing DNA ligase to join them together.

39
Q

What is SOS repair?

A

SOS repair is an emergency repair mechanism whereby error-prone DNA polymerases are attracted to replication forks that have become stalled at sides of unrepaired, damaged nucleotides. There, the error-prone polymerases add random nucleotides to the strand being synthesized opposite the damaged bases. This allows cells with damaged DNA to divide, but it is highly mutagenic (3/4 chance each added base pair).

40
Q

What process does homologous recombination mirror?

A

Meiotic recombination of homologous chromosomes.

41
Q

What are Holliday junctions?

A

X-shaped structures formed by two non-sister chromatid DNA strands overlapping during homologous recombination.

42
Q

What is a heteroduplex?

A

It forms when two non-sister chromatid DNA strands hydrogen bond to each other.

Genetics (MDSC 341) (7 decks)

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