Questions and Answers
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 type of damage occurs when reactive oxygen species attack DNA?
What is the major product of DNA oxidation?
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What type of radiation can cause DNA damage?
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What occurs when pyrimidines are exposed to UV light?
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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?
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What type of dimer is formed as a result of UV radiation?
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What mechanism normally detects and repairs replication errors?
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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?
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What is the effect of intercalating agents on DNA structure?
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What is the purpose of DNA repair mechanisms?
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What type of repair strategy involves the direct reversal of DNA lesions?
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What is an example of a base analog?
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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?
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What is the purpose of the mismatch repair system?
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What is the characteristic of the Homologous recombination repair mechanism?
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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?
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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?
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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?
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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?
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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?
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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?
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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?
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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?
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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.