CHP 7: mutation

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Match each mutagen to its category:

-5-Bromouracil matches Base analog -Hydroxylamine matches Hydroxylating agent -Ethylmethane sulfonate matches Alkylating agent -Nitrous acid matches Deaminating agent -Proflavin matches Intercalating agent

Match each mutagen to its mechanism of action:

-5-Bromouracil matches Is incorporated into DNA instead of thymine, but can pair with guanine -Hydroxylamine matches. Adds -OH to cytosine, allowing it to pair with adenine. -Ethylmethane sulfonate matches Adds an ethyl group to guanine, which then pair incorrectly -Nitrous acid matches Deaminates cytosine and adenine, changing their pairing properties -Proflavin matches Intercalates into the double helix, causing deletions and insertions

symptoms of Huntington disease:

-Cognitive decline -Muscle coordination difficulties

replica plating

A method of identifying bacterial colonies that have certain mutations by transferring cells from each colony on a master plate to a second (replica) plate and observing their growth when exposed to different conditions.

What is our current estimate of the rate of spontaneous mutations in eukaryotic organisms?

About 10-6 mutations per gene per gamete

Consider the following change in a DNA sequence (for simplicity only one of the DNA strands is written): 5'-AATGTGGATG-3' to 5'-AATGTGCATG-3'. What type of mutation is this?

Base substitution

When changes in DNA appear, they are initially considered "potential" mutations. Why?

Because most of them are repaired before the altered DNA is replicated

How does proflavin cause mutations?

By intercalating between base pairs

In polyQ trinucleotide repeat expansion disorders, the repeat sequence is...

CAG

forward mutation

Changes the wild-type phenotype to a mutant phenotype

Base excision repair relies on enzymes called ____ ____ that cleave altered bases from the sugar of their nucleotide.

DNA glycosylases

A mouse has a mutation in the DNA polymerase gene that impairs its 3'-to-5' exonuclease domain. What consequence would you expect?

DNA replication will have a higher error rate.

What particularly dangerous kind of DNA damage can be caused by X-rays?

Double-strand breaks

Which of the following statements accurately describes nonhomologous end-joining (NHEJ)?

During NHEJ the two broken ends of DNA are directly attached back together.

Which of the following statements accurately describes the relationship between DNA replication and mutation?

Even though DNA replication is very accurate, it can introduce errors, typically, less than once in every 109 base pairs.

Why are several forms of cancer associated with defects in DNA repair systems?

Failure of DNA repair allows mutations to accumulate that can lead to unregulated cell division.

What would be the expected characteristics of a mutagen that acts as an intercalating agent?

Flat, planar molecule

What was the first step in Muller's Drosophila experiment that demonstrated the mutagenic effects of X-rays?

He exposed male flies to X-rays and mated them to females which had a Balancer chromosome carrying a mutation causing Bar eyes.

Which of the following accurately describes a mechanism by which spontaneous heritable mutations can appear?

In order for a heritable mutation to appear, DNA must be altered and replicated before it is repaired.

What is one of the main determinants of the mutation rate of a particular gene?

Length of the coding sequence

If the proofreading ability of DNA polymerase fails and it inserts the wrong base, which of the following is most likely to be able to fix the resulting mutation?

Methyl-directed mismatch repair

Which of the following statements accurately compares the mutation rates of bacteria with those of multicellular eukaryotes?

Multicellular eukaryotes have higher mutation rates because many chances exist for mutations to accumulate in germ-line cells.

What best explains why multicellular organisms have a higher mutation rate than bacteria?

Mutations may occur at multiple stages of development before gametes form.

What is necessary for the cell to enzymatically correct a thymine dimer?

Photolyase, chromophore, and light

One type of error-prone DNA repair involves "sloppy" DNA polymerases that are attracted to stalled replication forks where they add random nucleotides. This type of DNA repair is known as the...

SOS system

What type of error-prone DNA repair involves "sloppy" DNA polymerases that are attracted to stalled replication forks, where they insert random nucleotides?

SOS system

Assume thymine was in its rare tautomeric state when DNA polymerase used it as a template during replication. After a second round of replication, the result would be a

TA to CG mutation in one of the four daughter molecules

Which test is used to evaluate the mutagenicity of an agent?

The Ames test

Of two genes, which should be easiest to mutate in a mutant screen?

The longest one

What accounts for the low error rate in DNA replication?

The polymerase has a 3'-to-5' exonuclease.

Why are mutations in somatic cells important?

They can affect genes that regulate cell growth and division and therefore cause cancer.

Double-strand breaks are typically repaired by...

_Homologous recombination repair _Nonhomologous end-joining

The organism used in the Ames test is...

a bacterium

A base tautomerization usually leads to a

a base substitution

Base excision repair is the main system used in the repair of...

abnormal bases

Alkylating agents cause mutations by

adding methyl or ethyl groups that disrupt base pairing

Hydroxylating agents mutate DNA by ______ a(n) ______ group to(from) cytosine, which allows it to pair with adenine.

adding; -OH

A mutagen is a

agent that causes mutations

Nitrous acid removes a(n) ____ group from adenine or cytosine, changing the bases to which they can pair. This leads to mutations in the newly-synthesized DNA strand during DNA replication.

amine

Certain compounds have a structure similar to normal DNA bases and so can be incorporated into daughter strands during DNA replication. These compounds are called base...

analogs

Nucleotide excision repair (NER) is the main system used in the repair of

base alterations that cannot be repaired by base excision

In humans, the normal HD+ allele has _____.

between 6 and 28 CAG repeats

Mutagens are sometimes called ____ because mutations cause cancer.

carcinogen

The Ames test assays whether a chemical agent...

causes mutations

The removal of a purine from DNA is called...

depurination

The breakage of chromosomes is referred to as a...

double stranded break

a mutation can result in the mutant allele being...

either recessive or dominant to the original wild-type allele.

When a mutant allele specifies a protein with functions qualitatively different from those of the corresponding wild-type protein, it is called a

gain-of-function allele

In humans, the mutant HD allele is considered a _____.

gain-of-function mutant allele

Proteins associated with polyQ trinucleotide repeat expansion disorders contain long tracts of the amino acid...

glutamine

A mutant allele is best defined as an allele that ______.

has a different DNA sequence from the wild-type

Mutation

heritable change in the base-pair sequence of DNA

Base analogs induce mutations by

incorporation into DNA instead of normal bases and tautomerization

Alkylating agents covalently attach _____or_____ groups to DNA bases, and thus disrupt their normal base pairing properties.

methyl or CH3

During DNA replication, a base that does not obey the normal base pairing rules is added. This type of replication error will most likely be corrected by....

methyl-directed mismatch repair

Deaminating agents like nitrous acid cause mutations by

modifying bases and thus altering their normal base-pairing properties

An agent that can change DNA structure and cause mutations is known as a...

mutagen

Altered bases that cannot be recognized by any of the cellular glycosylases are removed primarily by a DNA repair system called...

nucleotide excision repair

In most organisms (for example, bacteria or humans), the rate of spontaneous mutations introduced during DNA replication is less than ____.

once in 109 base pairs

The enzyme that can recognize thymine dimers and split them is called ____ . The enzyme that can remove methyl and ethyl groups from guanine is called ____

photolyase: akyltransferase

In his experiments with Drosophila, Muller exposed male flies to increasingly large doses of X-rays and mated them to females that had a Bar-marked Balancer X chromosome. Bar-eyed F1 females carrying a paternal X chromosome with a lethal mutation would _______.

produce sons only with Bar eyes

A temporary change in the structure of a nitrogen base due to movement of hydrogen atoms is called a(n)

tautomerization

A temporary change in the structure of a nitrogen base due to movement of hydrogen atoms is called a...

tautomerization

A tautomerization is a

temporary change in base structure

Unstable trinucleotide repeats are repeated sequences of three bases

that can increase or decrease in number generation after generation

____is a type of base substitution that involves a change of a pyrimidine to another pyrimidine, or a purine to another purine.

transition

Repeated sequences of three bases that can change in number generation after generation are called unstable...

trinucleotide repeats

The Ames test uses a strain of the bacterium Salmonella typhimurium that is...

unable to produce histidine

spontaneous mutations occur at a...

very low rate


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