DNA Damage and Repair Flashcards
Deletion or insertion mutations can be causes of mutations because they might displace the triplet codon reading frame of mRNA, which can vastly alter the formation of the intended protein.
frameshift
A mutation is when a single nucleotide alteration changes the original triplet codon sequence of mRNA to code for a different amino acid.
missense
In the lac operon under conditions of low , adenylate cyclase activity generates cAMP from ATP, which activates catabolite activator protein (CAP), leading to increased transcription.
glucose
(Conservative/Nonconservative) mutations are when the new amino acid that is produced via a missense mutation has similar chemical properties to the original amino acid.
conservative
A nonsense mutation is one in which the DNA alteration causes a codon that normally codes for an amino acid to change into a (start/stop) codon.
stop
A mutation in which the altered codon sequence codes for the same original amino acid is known as a mutation.
silent
A mutation is a change in one nucleotide in a gene sequence.
point
In conditions of high , repressor protein unbinds from repressor/operator site resulting in increased transcription of the lacZ, Y, and A genes.
lactose
Induced mutations are caused by (random chance/the environment) .
environment
The is an operon required for the transport and metabolism of lactose in Escherichia coli and many other enteric bacteria.
lac operon
A mutation in which the codon CGU is altered to CGA but the same amino acid is still inserted into the polypeptide chain would be which type of mutation?
Silent mutation
A silent mutation is a point mutation (alteration of a single nucleotide base) that does not cause a change in the amino acid that the codon codes for.
Point mutations of the 3rd or “wobble” position of a codon can allow silent mutations as multiple codons can code for the same amino acid, a concept known as redundancy. This helps maintain the integrity of the polypeptide.
Key Takeaway:
Silent mutations are point mutations that do not cause a change in the amino acid inserted into the polypeptide. The 3rd or “wobble” position is where many silent mutations occur.
Redundancy is the concept that multiple codons can code for the same amino acid, thus allowing for silent mutations.
Which of the following types of point mutation results in a different amino acid being inserted into the polypeptide chain?
missense mutation
A point mutation that results in a different amino acid being placed into the growing polypeptide chain is known as a missense mutation. Sickle cell disease is an example of a missense mutation that occurs when valine is inserted instead of glutamate.
Key Takeaway:
A point mutation that results in a different amino acid being placed into the growing polypeptide chain is known as a missense mutation.
Which of the following mutations causes premature termination of a polypeptide chain during translation?
nonsense mutation
A nonsense mutation is a point mutation that occurs when an incorrect mRNA nucleotide results in a UAA, UAG, or UGA codon. These are stop codons that signal early termination of the polypeptide chain.
Which of the following mutations will result in misreading of all codons downstream of the mutation?
frameshift
Frameshift mutations involve deletions or insertions of nucleotides in an mRNA sequence that are not multiples of 3. This causes codon sequence misreading downstream from the mutation.
When a base or bases are inserted or deleted from a sequence, the downstream sequences will be moved out of the correct order. This leads to significant changes in all subsequent codons, leading to many incorrect amino acids being coded for.
Key Takeaway:
Frameshift mutations involve deletions or insertions of nucleotides in an mRNA that are not multiples of 3. This causes codon sequence misreading downstream from the mutation.
Which of the following is an example of anticipation?
trinucleotide repeat expansions
Anticipation is seen in diseases that involve trinucleotide repeat expansions (e.g., Huntington’s disease). These trinucleotide repeats increase in length and contribute to earlier onset and severity of disease with each successive generation.
Key Takeaway:
Anticipation involves repeating codons (trinucleotide repeats) that increase and result in more severe disease with each successive generation.
Which of the following causes thymidine dimers?
Ultraviolet (UV) radiation
Ultraviolet (UV) radiation is absorbed by double bonds of pyrimidine bases (thymidine or cytosine). This energy can open the bond and allow it to react with adjacent pyrimidine bases in DNA and form covalent bonds.
These lesions are usually quickly fixed. However, uncorrected lesions over time can predispose individuals to further mutations (BRAF mutation in melanoma).
Key Takeaway:
UV radiation causes pyrimidine (thymidine and cytosine) dimers in DNA.
Which of the following are the enzymes involved in nucleotide excision repair?
- Endonuclease: removes damaged bases.
- DNA polymerase: Adds new bases to the areas where damaged bases were removed.
- DNA ligase: Links new bases to the DNA.
Nucleotide excision repair (NER) fixes bulky defects that distort the DNA helix, most commonly caused by pyrimidine dimers caused by UV radiation. Enzymes involved include:
Endonuclease: removes damaged bases.
DNA polymerase: Adds new bases to the areas where damaged bases were removed.
DNA ligase: Links new bases to the DNA.
[Choice A]: Glycosylase, lyase, and DNA ligase are enzymes involved in base excision repair (BER). BER is used when there is DNA damage caused by alkylation, deamination, and oxidation.
A patient has recurrent blistering of the skin that occurs within 15 minutes of going outside. A defect in which of the following repair pathways is most likely?
Nucleotide excision repair
Xeroderma pigmentosum is an autosomal recessive defect in the nucleotide excision repair pathway. Presentation involves sunlight intolerance and skin blistering within 15 minutes of sun exposure.
Without proper functioning of excision repair, DNA is susceptible to UV radiation (non-ionizing radiation) damage, particularly the formation of pyrimidine dimers.
Key Takeaway:
Xeroderma pigmentosum is a defect in the nucleotide excision repair pathway that results in severe intolerance to sunlight.
Defects in nucleotide excision repair increase the risk of which of the following conditions?
melanoma
People with nucleotide excision repair defects are susceptible to DNA damage from UV radiation. They are therefore at an increased risk for skin malignancies such as melanoma.
Key Takeaway:
Defects in nucleotide excision repair is associated with an increased risk for skin malignancies such as melanoma.
Which of the following mechanisms is responsible for repairing damage to DNA done by alkylation, deamination, and oxidation?
Base excision repair
Base excision repair is the DNA repair mechanism responsible for repairing damage caused by deamination, alkylation, and oxidation.
What is the correct order of enzyme activity in base excision repair?
D
- The steps of base excision repair are as follows
- Glycosylase: Removes the damaged base and creates an AP site.
- AP endonuclease: Cleaves the 5’ end to remove nucleotides.
- Lyase: Cleaves the 3’ end of the phosphate backbone.
- DNA polymerase B: Adds new bases to the 3’ end of DNA.
- DNA ligase: Links the new nucleotides with the existing DNA strand.
Mnemonic: The order of steps in base excision repair can be remembered with the phrase “GEL PLease”: Glycosylase, AP Endonuclease, Lyase, DNA Polymerase, DNA Ligase.
Which of the following is the most common inheritance pattern of familial adenomatous polyposis?
autosomal dominant mutation of the APC gene.
The most common genetic defect associated with familial adenomatous polyposis (FAP) is an autosomal dominant mutation of the APC gene.
An autosomal recessive defect in base excision repair is a less common mutation associated with FAP. Both of these defects result in significant colonic polyps and early-onset colorectal cancer.
Key Takeaway:
The most common mutation in FAP is an autosomal dominant mutation in the APC gene.
A less common mutation of FAP is an autosomal recessive defect in base excision repair.
Which of the following pathways repairs incorrect nucleotide placement during DNA replication?
DNA mismatch repair
DNA mismatch repair corrects mistakes involving nucleotide insertion during DNA replication.
Which of the following repair mechanisms is not cell cycle-dependent?
Base excision repair (BER)
Base excision repair (BER) is involved in the repair of DNA damage by deamination, oxidation, and radicals. It can occur throughout the entirety of the cell cycle and is not restricted to a specific phase.
Defects in mismatch repair is most associated with which of the following?
Lynch syndrome
DNA mismatch repair defects are associated with Lynch syndrome (hereditary nonpolyposis colorectal cancer), a disorder that predisposes patients to endometrial cancer, ovarian cancer, and nonpolyposis colorectal cancer.
Hereditary nonpolyposis colorectal cancer differs from familial adenomatous polyposis in that FAP will have thousands of colonic polyps while nonpolyposis colorectal cancer will have a limited number of polyps. FAP is most commonly associated with APC gene mutations (a gene involved in base excision repair).
Mnemonic: The high-yield cancer predispositions in Lynch syndrome can be remembered with CEO: Colorectal, Endometrial, Ovarian.
Key Takeaway:
Defects in DNA mismatch repair is associated with Lynch syndrome.
Which of the following repair mechanisms uses the sister chromatid as a template for repair?
Homologous recombination
Homologous recombination is a form of double-stranded DNA repair. It can only occur during late S phase or G2 phase, when DNA has been replicated and there are 2 homologous copies of each chromosome available.
During homologous recombination, the intact sister chromatid is used as a template to repair the broken chromatid. This allows for more accurate repair and less loss of DNA.
Key Takeaway:
Homologous recombination uses the sister chromatid of the broken DNA as a template to carry out accurate repair.
Breast and ovarian cancer is most likely to result from which of the following mutations?
BRCA1 mutation
The BRCA1 mutation results in the inability to perform homologous recombination repair. This defect leads to a high risk of developing ovarian and breast cancer.
Which of the following involves a defect in homologous recombination that results in skeletal abnormalities?
Fanconi anemia
Fanconi anemia results from a defect in homologous recombination.
Fanconi anemia has a variety of manifestations, with many involving bone tissue. These manifestations include aplastic anemia, bone marrow failure, skeletal abnormalities, and acute myelogenous leukemia.
Other manifestations of Fanconi anemia include café-au-lait spots, kidney abnormalities, intellectual disability, and hydrocephalus.
Nonhomologous end joining can occur during which of the following phases of the cell cycle?
All phases of the cell cycle
Nonhomologous end joining is a form of double-stranded DNA repair that does not require a sister chromatid template. As it does not require a template, this repair mechanism can occur throughout the entirety of the cell cycle, and it is also more error-prone than homologous recombination.
Which of the following conditions involves defective nonhomologous end joining?
Ataxia-telangiectasia
Ataxia-telangiectasia results from a mutation in the ATM gene, leading to a defect in the nonhomologous end joining repair pathway.
Mnemonic: Signs/symptoms of ataxia-telangiectasia can be remembered with the 5 A’s:
* Autosomal recessive ATM mutation
* IgA deficiency
* ↑ Alpha-fetoprotein levels (AFP)
* Ataxia
* Angiomas
[Choices A, B, and D]: Fanconi anemia, Bloom syndrome and BRCA1 mutation all involve defects in homologous recombination.
Key Takeaway:
Ataxia-telangiectasia involves a defect in nonhomologous end joining.
Which of the following mutations is most associated with recurrent sinopulmonary infections and spider angiomas?
ATM gene
The ATM mutation results in ataxia-telangiectasia, which includes findings such as ataxia, telangiectasia, spider angiomas, and immunodeficiency.
Immunodeficiency in ataxia-telangiectasia involves decreased B and T cells and deficiencies in IgA, IgE, and IgG. Immunoglobulin deficiencies, specifically IgA, increase susceptibility to recurrent infections of the sinopulmonary systems.
Mnemonic: Signs/symptoms of ataxia-telangiectasia can be remembered with the 5 A’s:
Autosomal recessive ATM mutation
IgA deficiency
↑ Alpha-fetoprotein levels (AFP)
Ataxia
Angiomas
Key Takeaway:
Patients with ataxia-telangiectasia are deficient in IgA and susceptible to recurrent sinopulmonary infections.
