Genetics (BIOL 450) Chapter 15

Which of these are reactive oxygen species that causes oxidative damage?

-OH O2 H2O2

Put these processes in the correct order for the base excision repair mechanism. (1) DNA glycosylase cuts a base-sugar bond. This results in either an apurinic or apyrimidinic site. (2) DNA polymerase fills in the missing stretch of DNA using the complementary DNA strand as a template. (3) Base damage is detected. (4) AP endonuclease nicks the damaged DNA strand upstream of the damage site. (5) DNA ligase links the phosphate-sugar backbone of the newly synthesized DNA segment with the remainder of the existing strand. (6) Deoxyribophosphodiesterase removes a stretch of DNA from the damaged DNA strand.

3, 1, 4, 6, 2, 5 After the damage is detected, the damage is cut out and removed. Then, polymerase fills in the missing spot and ligase glues the backbone back together.

A frameshift mutation changes the reading frame of a protein-coding gene. Which of these may NOT result from a frameshift mutation?

A frameshift mutation may result in a change in the phenotype of an organism, depending on the role of the affected protein. A change in the type of organism would not occur.

The _____ provides a method to screen compounds for their health and environmental risks by evaluating the level of mutagenicity of the compounds.

Ames test

Which of these statements is TRUE?

As a result of depurination, a guanine base can be lost from a DNA molecule. Depurination is the loss of a purine base, either guanine or adenine.

What are the types of point mutations in DNA?

Base Deletion Base Insertion Base Substitution

_____ are mutations in which one base pair is replaced by another.

Base substitutions

Delbrück Test

Delbrück codesigned the fluctuation test.

DNA damage can occur as a result of exposure to chemicals or ultraviolet radiation. What happens during nucleotide excision repair of damaged DNA?

Enzymes open the DNA strand, remove a segment of DNA from the strand that contains the damage, and resynthesize the correct DNA sequence.

_____ are flat molecules that fit between nucleotide bases that can cause an insertion or deletion.

Intercalating agents

How do proflavin and acridine orange differ from other mutagenic compounds?

Intercalating compounds such as proflavin and acridine orange differ from other mutagenic compounds in that they distort the DNA duplex "fooling" DNA polymerase into inserting extra bases or skipping templated bases, leading to base insertions and deletions, respectively, rather than base substitutions.

Select which examples are induced mutations. (Induced mutations occur when a cell is either accidentally or deliberately exposed to a mutagen.)

Ionizing radiation causes chromosomal fragmentation. Nitrous acid causes the deamination of cytosine to uracil.

How does homologous recombination repair double‑strand breaks in DNA?

It uses complementary sequence on a homologous chromosome as a template to extend DNA ends past a breakpoint.

Why is the loss of the mismatch repair pathway associated with specific types of cancer?

Loss of the MMR pathway increases the mutation frequency up to 100-fold and, like defects in other repair pathways, is associated with specific types of cancer.

Mismatched bases can be repaired by which molecular mechanism?

MMR (mismatch repair) can recognize and repair mismatched bases and small loops.

What mutation changes the sequence of the codon to one that codes for a different amino acid?

Missense Mutation

How does cancer differ from most other genetic disorders?

Most genetic disorders are inherited through germ cells from parents. Most cancers are, to some extent, the result of mutations in somatic cells that occur during an organism's lifetime.

What two major processes are responsible for genetic variation?

Mutation and recombination

_____ are changes in the sequence of DNA that cannot be repaired.

Mutations

Which pathway relieves replication and transcription blocks caused by bulky adducts?

Nucleotide excision repair (NER) pathways relieve replication and transcription blocks by repairing the damaged DNA.

An individual carries a mutation affecting the XPC protein. It is likely that in this person, _____ would proceed normally.

TC-NER

Depurinated sites can be repaired by which molecular mechanism?

TLS (translesion synthesis) can repair depurinated sites, bulky adducts, and pyrimidine dimers.

Ames's work identified carcinogens by observing which compounds or their associated metabolites could cause mutant bacteria to revert to a wild-type phenotype.

The Ames test is used to determine the mutagenic activity of chemicals by testing whether they increase the frequency of mutations in bacteria.

You are a physician. A woman brings her toddler to you because his mental development seems to be impaired. You run a battery of genetic tests on both the parents and the child to determine whether the child has a hereditary disease. The results show that the mother has 50 FMR-1 trinucleotide repeats, the father has 196 FMR-1 trinucleotide repeats, and the child has 546 FMR-1 trinucleotide repeats. What do you NOT conclude?

The mother does not carry a premutation for fragile X syndrome. Normal individuals have fewer than 45 CGG repeats, and the mother has 50, so the mother does carry a premutation for fragile X.

Point Mutation

a single-base-pair change in DNA sequence

A fully mutated FMR1 gene will have more than 200 repeats. In this case, its phenotype will be _____, transmission will be _____, it _____ be methylated, and transcription _____ take place.

affected; unstable, prone to expansion; will; will not

Base substitutions

are mutations in which one base pair is replaced by another. They can be divided into two subtypes: transitions and transversions

To overcome the problem that some metabolites of compounds are mutagenic agents and the compounds themselves are not mutagens, Ames used special strains of _____ that had mutant alleles for genes that synthesized histidine.

bacteria

Some chemical compounds are sufficiently similar to the normal nitrogenous bases of DNA that they are occasionally incorporated into DNA in place of normal bases; such compounds are called:

base analogs.

Which is not a potential consequence of a point mutation in the open reading frame of a gene? a. No change occurs in the amino acid sequence. b. A change to another amino acid. c. A change to a stop codon. d. Change in ionization

d. Change in ionization

A water molecule is added to adenine across a double bond. As a result, NH2 is replaced with a carbonyl group (=O) and a hydrogen is added to a nitrogen. The second hydrogen is added to NH2 to produce NH3, ammonia. Which type of spontaneous mutation has occurred?

deamination

Adenine is converted to hypoxanthine by what mechanism?

deamination

examples of how fragile sites can be responsible for phenotypic abnormalities

decreased gene dosage resulting from damage‑induced copy loss loss of gene function due to centromere loss increase in incidence of cancer due to disruption of tumor suppressor genes

Nucleotide excision repair corrects DNA damage due to UV light and bulky adducts by global genome and transcription-coupled mechanisms that each involve six steps:

detection, strand separation, incision, excision, synthesis, and ligation

Which of these cells can undergo germ-line mutations?

egg cells

IR can break _____ bonds, leading to the formation of apurinic (AP) sites or apyrimidinic (AP) sites (more generally called abasic sites).

glycosidic IR can break glycosidic bonds, which are covalent bonds that join a carbohydrate molecule to another group.

Collectively, base insertions and deletions are termed

indel mutations (for insertion-deletion)

Several mutagens can cause base damage. Such base damage includes photoproducts, thymine glycol, and apurinic or apyrimidinic sites. Which of these is NOT a mutagen that could cause base damage?

infrared light Ultraviolet light is a mutagen, while infrared light is not a common mutagen.

A base insertion

is the addition of one base pair

base deletion

is the removal of one base pair.

Premutation CGG size for the FMR1 gene is 55-200 repeats. In this case, its phenotype will be _____, transmission will be _____, it _____ be methylated, and transcription _____ take place.

largely normal; unstable; prone to expansion; will not; will A premutated FMR1 phenotype would be largely normal, transmission will be unstable, it will not be methylated, and transcription will take place.

All of these are types of DNA damage, EXCEPT:

methylation.

Guanine is converted to 8-oxoguanine by what mechanism?

oxidative damage

A spontaneous lesion caused by a reactive oxygen species is called:

oxidative damage.

The term _____ refers to a single base-pair change in DNA sequence.

point mutation

A point mutation in a noncoding region of a gene can affect expression of the encoded RNA by altering binding sites for _____.

proteins and RNAs

Thirty percent of human cancers are driven by mutations in ____

ras

Transition Subtype

replaces a purine with a purine (from A to G or G to A) or a pyrimidine with a pyrimidine (from C to T or T to C). There are four possible transitions.

Transversion Subtype

replaces a pyrimidine with a purine (from C to A, C to G, T to A, or T to G) or a purine with a pyrimidine (from A to C, A to T, G to C, or G to T). There are eight possible transversions.

Select the causes for potential errors in DNA replication.

replication slippage due to looping out of bases during replication of repetitive DNA mismatching due to wobble pairing of bases (occur naturally and spontaneously)

The loss of a purine base, or depurination, in DNA due to the disruption of the bond between a base and a deoxyribose sugar is one kind of:

spontaneous lesion.

Use the Mutations interactive to answer the question. Consider the adenine of the start codon to be position +1. Determine which of the mutations are nonsense mutations. a G nucleotide insertion between positions +12 and +13 in the antisense strand a transversion of C to A in the sense strand of the threonine codon the T nucleotide is deleted at position +5 in the antisense strand a transition at position +4 in the sense strand of the histidine codon substitutions of T to A at position +10 and G to T at position +11 in the antisense strand a transition from G to A in the sense strand of the tryptophan codon

substitutions of T to A at position +10 and G to T at position +11 in the antisense strand a transition from G to A in the sense strand of the tryptophan codon (These will result in a stop codon mutation, causing an early termination to the translation)

What are mechanisms of mutagens?

to damage a base in DNA so that it no longer pairs to alter a base in DNA so that it mispairs to replace a base in DNA

Glutamine is encoded by CAA and CAG codons. If a normal CAA codon is mutated to CAC, the codon will produce histidine instead of glutamine. This is a _____ mutation.

transversion and missense A transversion replaces a pyrimidine with a purine or a purine with a pyrimidine. Missense mutations change the sequence of a codon to one that codes for a different amino acid.