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Questions and Answers
What is the primary function of reverse transcriptase in retroviruses?
What is the primary function of reverse transcriptase in retroviruses?
Which of the following best describes the activities of reverse transcriptase?
Which of the following best describes the activities of reverse transcriptase?
What is a significant characteristic of reverse transcriptase compared to DNA polymerases?
What is a significant characteristic of reverse transcriptase compared to DNA polymerases?
What happens to the viral genome during the RNase H activity of reverse transcriptase?
What happens to the viral genome during the RNase H activity of reverse transcriptase?
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What is the primary reason DNA repair mechanisms are necessary?
What is the primary reason DNA repair mechanisms are necessary?
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Which repair system involves the recognition and removal of mismatched bases?
Which repair system involves the recognition and removal of mismatched bases?
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What role do DNA glycosylases play in excision repair?
What role do DNA glycosylases play in excision repair?
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Which of the following is NOT a basic DNA repair mechanism?
Which of the following is NOT a basic DNA repair mechanism?
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What type of DNA damage can cause mutations if the repair system is overwhelmed?
What type of DNA damage can cause mutations if the repair system is overwhelmed?
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Which repair mechanism is primarily responsible for dealing with UV-induced pyrimidine dimers?
Which repair mechanism is primarily responsible for dealing with UV-induced pyrimidine dimers?
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What is a potential consequence of ineffective DNA repair mechanisms?
What is a potential consequence of ineffective DNA repair mechanisms?
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Which process is primarily involved in filling gaps after damaged bases are removed during excision repair?
Which process is primarily involved in filling gaps after damaged bases are removed during excision repair?
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In which phase of the cell cycle does mismatch repair primarily occur?
In which phase of the cell cycle does mismatch repair primarily occur?
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What type of DNA is characterized as having both methylated and unmethylated strands?
What type of DNA is characterized as having both methylated and unmethylated strands?
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What mechanical process is involved in the recognition of hemimethylated DNA?
What mechanical process is involved in the recognition of hemimethylated DNA?
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Which of the following represents a fully unmodified DNA strand?
Which of the following represents a fully unmodified DNA strand?
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What is the role of DNA repair enzymes related to tumor suppression?
What is the role of DNA repair enzymes related to tumor suppression?
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Which DNA repair mechanism is specifically involved in direct repair of UV-induced pyrimidine dimers?
Which DNA repair mechanism is specifically involved in direct repair of UV-induced pyrimidine dimers?
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What is the function of alkylating agents in relation to DNA?
What is the function of alkylating agents in relation to DNA?
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Which of the following repair mechanisms is involved in both homologous recombination (HR) and non-homologous end joining (NHEJ)?
Which of the following repair mechanisms is involved in both homologous recombination (HR) and non-homologous end joining (NHEJ)?
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Who were the 2015 Nobel Prize winners recognized for their work on DNA repair mechanisms?
Who were the 2015 Nobel Prize winners recognized for their work on DNA repair mechanisms?
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Which cells primarily utilize nucleotide excision repair (NER) to repair DNA damage caused by UV light?
Which cells primarily utilize nucleotide excision repair (NER) to repair DNA damage caused by UV light?
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What is the primary function of Nucleotide Excision Repair (NER)?
What is the primary function of Nucleotide Excision Repair (NER)?
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What is the primary process necessary for removing incorrect or damaged DNA bases?
What is the primary process necessary for removing incorrect or damaged DNA bases?
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Which of the following describes the role of light in the action of photolyase?
Which of the following describes the role of light in the action of photolyase?
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Which DNA repair mechanism is primarily involved in the repair of double-stranded breaks?
Which DNA repair mechanism is primarily involved in the repair of double-stranded breaks?
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During which biological process does homologous recombination primarily occur?
During which biological process does homologous recombination primarily occur?
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Which statement most accurately describes Non-Homologous End Joining (NHEJ)?
Which statement most accurately describes Non-Homologous End Joining (NHEJ)?
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What role do proteins play during homologous recombination?
What role do proteins play during homologous recombination?
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Which gene-editing technique relies on homologous recombination?
Which gene-editing technique relies on homologous recombination?
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What is a distinguishing feature of Nucleotide Excision Repair compared to other repair mechanisms?
What is a distinguishing feature of Nucleotide Excision Repair compared to other repair mechanisms?
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In which of the following scenarios would Non-Homologous End Joining be utilized?
In which of the following scenarios would Non-Homologous End Joining be utilized?
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What type of mutation occurs due to the alkylation of guanine at the O6 atom?
What type of mutation occurs due to the alkylation of guanine at the O6 atom?
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What enzyme is responsible for creating an abasic site during Base Excision Repair (BER)?
What enzyme is responsible for creating an abasic site during Base Excision Repair (BER)?
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Which statement accurately describes an AP site?
Which statement accurately describes an AP site?
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What role does Uracil Glycosylase perform in nucleotide deamination?
What role does Uracil Glycosylase perform in nucleotide deamination?
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Which enzyme is responsible for cleaving a region of DNA at an AP site?
Which enzyme is responsible for cleaving a region of DNA at an AP site?
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What differentiates mismatch repair from other DNA repair mechanisms?
What differentiates mismatch repair from other DNA repair mechanisms?
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Which of the following processes is involved in fixing an AP site?
Which of the following processes is involved in fixing an AP site?
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What happens to the DNA strand if the AP site is not repaired?
What happens to the DNA strand if the AP site is not repaired?
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Study Notes
DNA Repair
- DNA must be preserved, unlike other biomolecules like RNA, proteins, and lipids, which can be replaced.
- Cells use various repair mechanisms to address issues like missing or altered bases, bulges due to insertions or deletions, UV-induced pyrimidine dimers, strand breaks, and cross-links.
- Six primary DNA repair systems exist: mismatch repair, base excision repair (BER), nucleotide excision repair (NER), double-strand break repair (including non-homologous end joining), and direct repair.
- Mismatch repair fixes incorrectly paired bases.
- Excision repair removes damaged bases, sugar, and phosphate, and fills the gap with new material.
Rate of DNA Damage
- DNA is damaged at a high rate, from 192 cytosine deaminations to 55,000 single-strand breaks per cell per day.
- This damage also includes deurination/depyrimidinations and chemical alterations like 8-oxoG oxidation.
- The type of damage leads to different predominant mutations, from substitutions to chromosome rearrangements.
DNA Repair Mechanisms
- Mismatch repair is triggered by incorrectly paired bases and removes the mismatched area for re-replication.
- Excision repair removes damaged bases, the sugar and phosphate, and has a mechanism to replace the missing portion with correct material.
Damaging Agents
- Damaging agents include X-rays, oxygen radicals, alkylating agents, UV light, polycyclic aromatic hydrocarbons, and anti-tumor agents (e.g., Cis-Pt, MMC).
- Types of damage include single-strand breaks, uracil, abasic sites, 8-oxoguanine, and various cross-links.
Repair Processes
- Different repair processes address different types of damage.
- Base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR) and recombination and other mechanisms address varied types of damage.
Molecular Mechanisms for DNA Repair
- Direct reversal: a damaged base is directly reversed.
- Mismatch repair: enzymes recognize mismatches, remove the area, and re-replicate it correctly.
- Single-strand break repair (SSB): has several methods (including BER and NER), which remove the damaged region.
- Double-strand break repair (DSB): includes pathways like NHEJ, and HR for repairing the broken region.
Repair Systems in E. Coli and Human
- E. coli and human cells use various enzyme/protein complexes for repair mechanisms.
Nobel Prize for DNA Repair
- Tomas Lindahl, Paul Modrich, and Aziz Sancar won the 2015 Nobel Prize for their discoveries related to DNA repair mechanisms.
UV-induced Pyrimidine Dimers
- UV light induces the formation of pyrimidine dimers, which are covalent links between adjacent pyrimidine bases (e.g. between two thymines or two cT).
- UV-induced pyrimidine dimers warp the DNA helix structure preventing proper function and need repair.
Photolyase (Direct Repair)
- Photolyase is an enzyme that can directly repair UV-induced pyrimidine dimers.
- This repair requires UV light.
- It is found in bacteria and some lower eukaryotes but not in mammals.
Alkylating Agents
- Alkylating agents add alkyl groups to DNA bases.
- This modification causes mutations and can lead to various diseases.
- Alkylating agents have different functional mechanisms (mono- vs. bi-functional), impacting various DNA sequences.
Alkylation of Guanine
- Alkylation of guanine at the O6 atom is highly mutagenic.
- This is because it alters the base-pairing characteristics, resulting in a G-C to A-T transversion mutation.
Direct Repair in Eukaryotes (O6-methylguanine)
- Eukaryotic cells use different enzymes (like MGMT) for direct reversal of O6-methylguanine damage.
Base Excision Repair (BER)
- BER removes damaged DNA bases, such as uracil, through a step-by-step pathway.
- This pathway involves glycosylases, AP endonucleases, and DNA polymerases.
- The damaged base is removed, the gap repaired, and DNA ligase seals the break and the DNA is repaired.
Uracil Glycosylase
- Uracil glycosylase removes uracil bases from the DNA.
- Uracil is an incorrect base that should not normally be in DNA.
AP Endonuclease/Exonuclease
- AP endonuclease/exonuclease cleaves the DNA backbone at the site of an AP site (apurinic or apyrimidinic).
- Exonuclease removes damaged bases and nucleotides from the strand.
Nucleotide Excision Repair (NER)
- NER repairs bulky DNA lesions like pyrimidine dimers.
- The process involves a multi-step pathway, including recognizing the damage, unwinding the DNA, removing the damaged section, and replacing it with correct nucleotides.
- NER mechanisms differ significantly between bacteria and higher eukaryotes.
NER in Eukaryotes
- UV-DDB, XBP, XPD, XPF, and XPG are involved in damage recognition and repair in eukaryotic NER.
- TFIIH plays a key role in unwinding DNA at the damage site.
- The process of removal includes different protein complexes that cut the DNA at both 3´ and 5´ regions flanking the damage and fill the gap with the correct nucleotides using DNA polymerase and ligase.
DNA Double-Stranded Break Repair
- Two major pathways exist for repairing double-strand breaks in DNA: homologous recombination (HR) and non-homologous end joining (NHEJ).
Homologous Recombination
- Requires a sister chromatid or homologous chromosome for template repair.
- Involves several protein complexes for strand recognition, break repair, and the repair of the break, using a homologous sequence as a template.
- Mechanisms have several steps for repairing DNA correctly.
Non-Homologous End Joining (NHEJ)
- NHEJ directly joins DNA ends without the requirement of a homologous template.
- Several proteins are involved, including Ku proteins, DNA-PK, and others.
- NHEJ repair can result in errors and mutations.
DNA Methylation
- DNA methylation plays a crucial role in maintaining genomic stability and is a key part of the machinery for MMR.
- Methylation patterns are typically symmetrical and are maintained through replication.
Mut System
- The Mut system in E. coli recognizes hemimethylated DNA to identify the newly synthesized strand during replication for better repair.
- There are other DNA repair systems in Bacteria.
HIV Drugs
- Reverse transcriptase inhibitors are among drugs targeting the retroviral replication machinery to prevent HIV reproduction.
- Effective HIV treatments aim to selectively block reverse transcription to stop the replication cycle.
CRISPR
- CRISPR is a genome editing technology that uses a bacterial defense system to target and modify DNA sequences.
- It involves a bacterial protein Cas9 guided by an RNA sequence, and is commonly used to modify genes.
General
- DNA repair is a complex process carried out by an array of proteins and enzymes.
- Mutations can have significant impacts, varying from inconsequential effects to severe diseases, and the rate of DNA damage can influence disease risk.
- Mechanisms of DNA repair vary in different organisms and cell types.
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Description
Test your knowledge on the various DNA repair mechanisms and the rate of DNA damage. This quiz covers essential topics such as mismatch repair, base excision repair, and the consequences of DNA damage. Challenge yourself and learn more about these vital cellular processes!
