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Questions and Answers
What occurs as a result of the loss of a purine base by spontaneous hydrolysis of the N-glycosidic bond?
What occurs as a result of the loss of a purine base by spontaneous hydrolysis of the N-glycosidic bond?
What is the rate of depurination under physiological conditions?
What is the rate of depurination under physiological conditions?
What type of damage occurs when reactive oxygen species attack DNA?
What type of damage occurs when reactive oxygen species attack DNA?
What is the major product of DNA oxidation?
What is the major product of DNA oxidation?
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What type of radiation can cause DNA damage?
What type of radiation can cause DNA damage?
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What occurs when pyrimidines are exposed to UV light?
What occurs when pyrimidines are exposed to UV light?
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What is the result of thymine dimers in DNA?
What is the result of thymine dimers in DNA?
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What happens to a cell if it does not undergo repair after DNA damage?
What happens to a cell if it does not undergo repair after DNA damage?
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What type of dimer is formed as a result of UV radiation?
What type of dimer is formed as a result of UV radiation?
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What mechanism normally detects and repairs replication errors?
What mechanism normally detects and repairs replication errors?
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What is one way that ionizing radiation damages DNA molecules?
What is one way that ionizing radiation damages DNA molecules?
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What type of mutagen can induce mutations by changing the chemical structure of DNA bases?
What type of mutagen can induce mutations by changing the chemical structure of DNA bases?
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What is the effect of intercalating agents on DNA structure?
What is the effect of intercalating agents on DNA structure?
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What is the purpose of DNA repair mechanisms?
What is the purpose of DNA repair mechanisms?
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What type of repair strategy involves the direct reversal of DNA lesions?
What type of repair strategy involves the direct reversal of DNA lesions?
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What is an example of a base analog?
What is an example of a base analog?
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What is the reason behind the rarity of replication errors in DNA?
What is the reason behind the rarity of replication errors in DNA?
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What is the direction of the exonuclease activity of DNA polymerases?
What is the direction of the exonuclease activity of DNA polymerases?
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What is the purpose of the mismatch repair system?
What is the purpose of the mismatch repair system?
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What is the characteristic of the Homologous recombination repair mechanism?
What is the characteristic of the Homologous recombination repair mechanism?
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What is the consequence of unrepaired double-strand breaks?
What is the consequence of unrepaired double-strand breaks?
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What type of repair system is involved in correcting lesions that cause bulk distortions in DNA helix?
What type of repair system is involved in correcting lesions that cause bulk distortions in DNA helix?
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What happens to mutations if they are not corrected by DNA repair systems?
What happens to mutations if they are not corrected by DNA repair systems?
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Which enzyme is involved in direct repair and transfers a methyl group from G to a cysteine residue within the enzyme itself?
Which enzyme is involved in direct repair and transfers a methyl group from G to a cysteine residue within the enzyme itself?
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What is the result of the action of DNA-N-glycosylases in base excision repair?
What is the result of the action of DNA-N-glycosylases in base excision repair?
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What is the role of AP endonucleases in base excision repair?
What is the role of AP endonucleases in base excision repair?
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What is the consequence of a defect in nucleotide excision repair?
What is the consequence of a defect in nucleotide excision repair?
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What type of repair system corrects errors introduced during DNA replication?
What type of repair system corrects errors introduced during DNA replication?
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What is the duration of the DNA region removed during nucleotide excision repair?
What is the duration of the DNA region removed during nucleotide excision repair?
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What is the enzyme responsible for repairing UV-induced damage in plants, bacteria, and some animals?
What is the enzyme responsible for repairing UV-induced damage in plants, bacteria, and some animals?
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What type of mutation occurs when a single nucleotide base is altered in the DNA sequence?
What type of mutation occurs when a single nucleotide base is altered in the DNA sequence?
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What is the result of a nonsense mutation?
What is the result of a nonsense mutation?
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What type of mutation occurs when the number of nucleotides inserted or deleted is not a multiple of three?
What type of mutation occurs when the number of nucleotides inserted or deleted is not a multiple of three?
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What is a transition in the context of point mutations?
What is a transition in the context of point mutations?
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What type of mutation has no effect on the protein sequence?
What type of mutation has no effect on the protein sequence?
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What is the term for a missense mutation where the new amino acid is chemically similar to the original one?
What is the term for a missense mutation where the new amino acid is chemically similar to the original one?
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Study Notes
DNA Damage and Mutation
- DNA damage occurs through various mechanisms, including:
- Depurination: loss of purine bases due to spontaneous hydrolysis of N-glycosidic bonds, resulting in apurinic sites (AP sites)
- Replication errors: incorrect incorporation of nucleotides during DNA replication, leading to base pair deletions, insertions, or substitutions
- Oxidative damage: chemical modification of nitrogenous bases due to reactive oxygen species (ROS), resulting in mispairing
- Exogenous DNA damage: radiation and chemical mutagens
Exogenous DNA Damage
- Radiation damage:
- UV light: forms pyrimidine dimers (thymine dimers) through intra-strand crosslinking, altering DNA structure and preventing proper replication
- Ionizing radiation: causes direct damage to DNA molecules, producing single-strand breaks (SSBs) and double-strand breaks (DSBs), and indirect damage through production of free radicals
- Chemical mutagens:
- Base modifying agents: alter the chemical structure of DNA bases, leading to mispairing (e.g., alkylating agents like SAM)
- Base analogs: replace standard DNA bases, leading to base pair substitutions (e.g., 2-amino purine replacing adenine)
- Intercalating agents: insert themselves between adjacent DNA bases, affecting DNA structure and leading to frameshift mutations (e.g., acridine orange, benzopyrene)
DNA Repair Pathways
- Direct repair:
- Photolyases: repair UV-induced damage in plants, bacteria, and some animals (excluding humans) by splitting dimers
- O6-methylguanine methyltransferase: transfers a methyl group from G to a cysteine residue within the enzyme, repairing damage
- Base excision repair (BER):
- Enzymes like uracil DNA glycosylase recognize and remove damaged bases, resulting in AP sites
- AP endonucleases nick the damaged backbone, and DNA polymerase and ligase repair the region
- Nucleotide excision repair (NER):
- Corrects lesions causing bulk distortions in DNA helix, such as UV-induced pyrimidine dimers
- Involves recognition, excision, and resynthesis of the damaged region
- Strand-directed mismatch repair (MMR):
- Corrects errors introduced during DNA replication, such as base substitutions, deletions, and insertions
- Recognizes and corrects errors that escaped DNA polymerase proofreading machinery
- Double-strand breaks repair:
- Two types: non-homologous end joining (error-prone) and homologous recombination (error-free)
Mutations
- Frameshift mutation: alteration in the reading frame due to insertion or deletion of nucleotides
- Point mutation: alteration in a single nucleotide base, resulting in a change in a single base pair (substitution)
- Transition: replacement of one purine with another purine or one pyrimidine with another pyrimidine
- Transversion: replacement of one purine with one pyrimidine or vice versa
- Types of point mutations:
- Silent mutation: no effect on protein sequence
- Nonsense mutation: truncation of protein due to premature stop codon
- Missense mutation: alteration in amino acid sequence, potentially affecting protein function
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Description
This quiz covers the process of depurination, a spontaneous hydrolysis of the N-glycosidic bond that links purine bases to deoxyribose in DNA, and its consequences on DNA replication and mutation. Learn about the repair mechanisms of apurinic sites.