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Questions and Answers
What process generates two Holliday intermediates during DNA repair?
What process generates two Holliday intermediates during DNA repair?
What enzyme is primarily responsible for sealing nicks in the DNA after resolution of Holliday intermediates?
What enzyme is primarily responsible for sealing nicks in the DNA after resolution of Holliday intermediates?
What type of repair can begin after the undamaged complement is generated from the strand with a DNA lesion?
What type of repair can begin after the undamaged complement is generated from the strand with a DNA lesion?
How do most cells typically resolve the Holliday intermediates during DNA repair?
How do most cells typically resolve the Holliday intermediates during DNA repair?
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What role do recombinases play in the context of DNA repair?
What role do recombinases play in the context of DNA repair?
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What is the primary consequence of DNA lesions during replication?
What is the primary consequence of DNA lesions during replication?
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Which process allows DNA synthesis to continue over a lesion?
Which process allows DNA synthesis to continue over a lesion?
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What happens when a replication fork encounters a lesion undergoing nucleotide excision repair?
What happens when a replication fork encounters a lesion undergoing nucleotide excision repair?
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In which scenario does the replication machinery stall during DNA synthesis?
In which scenario does the replication machinery stall during DNA synthesis?
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What type of mutation can occur if an O6-meG lesion in the template strand is replicated?
What type of mutation can occur if an O6-meG lesion in the template strand is replicated?
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What typically happens when replication machinery is blocked by a lesion but resumes further downstream?
What typically happens when replication machinery is blocked by a lesion but resumes further downstream?
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What characterizes translesion DNA polymerases?
What characterizes translesion DNA polymerases?
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In normal conditions, when do most lesions cause replication forks to stall?
In normal conditions, when do most lesions cause replication forks to stall?
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What is the primary advantage of recombinational DNA repair over translesion DNA synthesis?
What is the primary advantage of recombinational DNA repair over translesion DNA synthesis?
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What occurs when a replication fork encounters a break in a template strand?
What occurs when a replication fork encounters a break in a template strand?
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What is the first step in the recombinational double-strand break repair when a replication fork collapses?
What is the first step in the recombinational double-strand break repair when a replication fork collapses?
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What does branch migration accomplish in the recombinational repair process?
What does branch migration accomplish in the recombinational repair process?
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What happens during fork regression when a replication fork stalls?
What happens during fork regression when a replication fork stalls?
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What is a Holliday intermediate?
What is a Holliday intermediate?
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What role does the dedicted replication restart complex play after repairing a replication fork?
What role does the dedicted replication restart complex play after repairing a replication fork?
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Which of the following DNA repair processes requires the lesion to occur in only one strand of duplex DNA?
Which of the following DNA repair processes requires the lesion to occur in only one strand of duplex DNA?
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What mechanism can be used for filling in single-stranded DNA regions left by DNA polymerase during replication?
What mechanism can be used for filling in single-stranded DNA regions left by DNA polymerase during replication?
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Which statement best describes branch migration?
Which statement best describes branch migration?
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What happens if a lesion is not repaired after forming a Holliday intermediate?
What happens if a lesion is not repaired after forming a Holliday intermediate?
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In what situation is recombinational DNA repair preferred over translesion DNA synthesis?
In what situation is recombinational DNA repair preferred over translesion DNA synthesis?
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Which enzyme is involved in the process of resolving the Holliday intermediate?
Which enzyme is involved in the process of resolving the Holliday intermediate?
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What initiates the repair of double-strand breaks (DSBs) in recombinational DNA repair?
What initiates the repair of double-strand breaks (DSBs) in recombinational DNA repair?
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Which enzyme class is essential for the DNA strand invasion step during homologous recombination?
Which enzyme class is essential for the DNA strand invasion step during homologous recombination?
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What structural intermediate is formed during the initial stages of DSB repair in recombinational DNA repair?
What structural intermediate is formed during the initial stages of DSB repair in recombinational DNA repair?
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What role do DNA polymerases play in the repair of DSBs?
What role do DNA polymerases play in the repair of DSBs?
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What does the pathway known as synthesis-dependent strand annealing (SDSA) involve?
What does the pathway known as synthesis-dependent strand annealing (SDSA) involve?
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What is a potential consequence of improper homologous recombination?
What is a potential consequence of improper homologous recombination?
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What is the function of Holliday junction resolvases?
What is the function of Holliday junction resolvases?
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What type of DNA structure is referred to as a Holliday intermediate?
What type of DNA structure is referred to as a Holliday intermediate?
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What happens to the breaks left by the cleavage of Holliday intermediates?
What happens to the breaks left by the cleavage of Holliday intermediates?
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During which phase is homologous recombination most likely to occur?
During which phase is homologous recombination most likely to occur?
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What does the term 'DSB repair' refer to specifically?
What does the term 'DSB repair' refer to specifically?
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What effect do oxidative DNA damage and ionizing radiation have on DNA?
What effect do oxidative DNA damage and ionizing radiation have on DNA?
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What is retained when both Holliday intermediates are cleaved at the same site during repair?
What is retained when both Holliday intermediates are cleaved at the same site during repair?
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Study Notes
DNA Replication and Repair Mechanisms
- DNA damage is common and detrimental, especially during replication. Damage impacts replication in various ways.
Outcomes of Lesions During Replication
- Translesion Synthesis (TLS): DNA synthesis continues over the lesion using specialized DNA polymerases. This is often the case with a lesion that doesn't significantly distort the DNA. A common result of TLS is a mutation.
- Lesion Repair and Fork Collapses: If repair is initiated but incomplete when the replication fork arrives, the fork collapses, creating a double-strand break (DSB). Recombinational repair fixes this.
- Replication Fork Stalling: Replisome halts at the lesion. Replication can restart downstream, leaving the lesion behind. The lesion is in a single-stranded gap. This is more common in delaying strand..
- Replication Bypass and Restart: The replication machinery halts but picks up again. The lesion is left behind, in a single-stranded gap. This bypass is more common on the lagging strand due to how Okazaki fragments are generated.
DNA Double-Strand Break Repair (DSBR)
- Double-strand breaks (DSBs) are lethal if not repaired. They can originate from oxidative damage or radiation.
- DSBR utilizes homologous recombination; requires an undamaged homologous DNA molecule, for example, a sister chromatid.
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DSBR Pathway:
- Broken DNA ends are processed.
- The 3’ strands invade the homologous chromosome.
- The invading strand is replicated.
- The invading strand is used for replication to restore the damaged piece of DNA using the homologous chromosome as a template.
- Repair pathways utilize recombination.
- The DNA double crossover intermediate has multiple resolution options.
- Synthesis-Dependent Strand Annealing (SDSA): The invading strands are displaced, and any gaps are filled.
- Double-Strand Break Repair (DSBR): The strands are linked until replication is completed, forming a Holliday intermediate. Holliday Junction Resolvases cleaves the Holliday intermediate in ways that retain or exchange the chromosomal DNA segments.
- The DNA double crossover intermediate has multiple resolution options.
Replication Fork Repair
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Collapsed Replication Forks: A broken template strand leads to a DSB. Recombinational repair recreates the replication fork. The steps are similar to DSBR.
- Broken DNA end is processed to create a single-stranded extension.
- The strand then invades the intact chromosome.
- Branch migration moves the branch point in one direction, usually.
- The branch can be resolved, and replication can restart without mutations..
- Stalled Replication Forks: The fork stops at the lesion. This triggers fork regression (fork moves backward) to bring the lesion into contact with its complementary strand. It results in a four-branched Holliday intermediate. It also allows further repair. This lesion can be repaired by DNA excision repair or other relevant pathways..
Gap Repair
- A lesion can cause single-stranded gap in which TLS fills in the missing DNA segment. If TLS is mutagenic, recombinational gap repair happens in another way.
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Gap Repair Pathway:
- A recombinase binds to the single-stranded gap.
- Recombinase promotes strand invasion into the undamaged double-stranded DNA of the replication fork.
- Branch migration generates Holliday intermediates.
- The displaced strand acts as a template allowing further DNA replication.
- The Holliday intermediates are resolved, resulting in non-crossover pathways, and gaps are filled. NER, BER can begin at the lesion.
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Description
Explore the essential processes of DNA replication and the various repair mechanisms that deal with DNA lesions. This quiz examines translesion synthesis, lesion repair, and the consequences of replication fork stalling. Test your knowledge on how cells manage DNA damage during replication!