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Questions and Answers
Which DNA repair mechanism directly reverses damage caused by UV radiation, utilizing light energy?
Which DNA repair mechanism directly reverses damage caused by UV radiation, utilizing light energy?
- Photoreactive Repair (correct)
- Base Excision Repair (BER)
- Mismatch Repair
- Nucleotide Excision Repair (NER)
During DNA replication, what enzymatic activity allows DNA polymerase to correct mismatched base pairs?
During DNA replication, what enzymatic activity allows DNA polymerase to correct mismatched base pairs?
- 3' to 5' exonuclease activity (correct)
- Methyltransferase activity
- 5' to 3' endonuclease activity
- Photolyase activity
Which DNA repair pathway involves removing a single damaged base, followed by replacing the entire nucleotide?
Which DNA repair pathway involves removing a single damaged base, followed by replacing the entire nucleotide?
- Photoreactive Repair
- Nucleotide Excision Repair (NER)
- Mismatch Repair
- Base Excision Repair (BER) (correct)
What is the primary characteristic of repair mechanisms that circumvent problems caused by mutations?
What is the primary characteristic of repair mechanisms that circumvent problems caused by mutations?
Xeroderma pigmentosum (XP) is a genetic disorder caused by defects in which DNA repair mechanism?
Xeroderma pigmentosum (XP) is a genetic disorder caused by defects in which DNA repair mechanism?
Which of the following organisms utilizes photoreactive repair?
Which of the following organisms utilizes photoreactive repair?
Which DNA repair mechanism involves the removal of a larger segment of a DNA strand that contains damaged nucleotides?
Which DNA repair mechanism involves the removal of a larger segment of a DNA strand that contains damaged nucleotides?
A cell with a mutation that inactivates the 3' to 5' exonuclease activity of its DNA polymerase would likely exhibit:
A cell with a mutation that inactivates the 3' to 5' exonuclease activity of its DNA polymerase would likely exhibit:
Which of the following mechanisms is MOST likely to be involved in correcting errors introduced during DNA replication that were missed by the proofreading activity of DNA polymerase?
Which of the following mechanisms is MOST likely to be involved in correcting errors introduced during DNA replication that were missed by the proofreading activity of DNA polymerase?
A researcher is studying a new bacterial strain and observes that it is highly susceptible to DNA damage from UV radiation. Further analysis reveals a defect in a repair mechanism that requires an intact complementary strand of DNA. Which repair pathway is MOST likely affected?
A researcher is studying a new bacterial strain and observes that it is highly susceptible to DNA damage from UV radiation. Further analysis reveals a defect in a repair mechanism that requires an intact complementary strand of DNA. Which repair pathway is MOST likely affected?
A scientist is investigating a cellular response to a chemotherapeutic agent that induces double-strand breaks (DSBs) in DNA. They observe that cells are still able to repair the DNA, but with a noticeable increase in small insertions and deletions at the repair site. Which repair mechanism is MOST likely responsible for this observation?
A scientist is investigating a cellular response to a chemotherapeutic agent that induces double-strand breaks (DSBs) in DNA. They observe that cells are still able to repair the DNA, but with a noticeable increase in small insertions and deletions at the repair site. Which repair mechanism is MOST likely responsible for this observation?
Following exposure to a DNA damaging agent, a cell activates several DNA damage-signaling pathways. What is the PRIMARY purpose of these signaling systems?
Following exposure to a DNA damaging agent, a cell activates several DNA damage-signaling pathways. What is the PRIMARY purpose of these signaling systems?
In which of the following scenarios would Synthesis-Dependent Strand Annealing (SDSA) be the MOST appropriate mechanism for repairing a double-strand break (DSB)?
In which of the following scenarios would Synthesis-Dependent Strand Annealing (SDSA) be the MOST appropriate mechanism for repairing a double-strand break (DSB)?
A clinical study identifies a correlation between mutations in genes involved in Nucleotide Excision Repair (NER) and increased susceptibility to skin cancer. Which of the following is the MOST likely explanation for this observation?
A clinical study identifies a correlation between mutations in genes involved in Nucleotide Excision Repair (NER) and increased susceptibility to skin cancer. Which of the following is the MOST likely explanation for this observation?
Which of the following repair mechanisms directly reverses DNA damage, rather than removing and replacing the damaged nucleotides?
Which of the following repair mechanisms directly reverses DNA damage, rather than removing and replacing the damaged nucleotides?
A researcher discovers a novel mutation that disrupts the function of a specific DNA glycosylase. Which DNA repair pathway would be MOST directly affected by this mutation?
A researcher discovers a novel mutation that disrupts the function of a specific DNA glycosylase. Which DNA repair pathway would be MOST directly affected by this mutation?
Which of the following best describes the immediate consequence of DNA intercalation by agents like proflavine or benzo[a]pyrene?
Which of the following best describes the immediate consequence of DNA intercalation by agents like proflavine or benzo[a]pyrene?
Ionizing radiation is a potent mutagen because it possesses:
Ionizing radiation is a potent mutagen because it possesses:
Considering the impact of mutations, why is the existence of some unrepaired mutations necessary for species?
Considering the impact of mutations, why is the existence of some unrepaired mutations necessary for species?
Which statement accurately describes the relationship between DNA repair mechanisms and the occurrence of mutations?
Which statement accurately describes the relationship between DNA repair mechanisms and the occurrence of mutations?
If a cell lacked the ability to perform DNA repair, what would be the most likely consequence?
If a cell lacked the ability to perform DNA repair, what would be the most likely consequence?
A scientist is studying a new chemical mutagen. After exposing cells to the mutagen, they observe a significant increase in the number of DNA double-strand breaks. Which DNA repair pathway is most likely to be involved in repairing this type of damage?
A scientist is studying a new chemical mutagen. After exposing cells to the mutagen, they observe a significant increase in the number of DNA double-strand breaks. Which DNA repair pathway is most likely to be involved in repairing this type of damage?
Why is UV radiation a greater mutagenic concern than other forms of energy above the visible spectrum?
Why is UV radiation a greater mutagenic concern than other forms of energy above the visible spectrum?
A researcher discovers a new mutation in a bacterial strain that increases its resistance to UV radiation. Further analysis reveals that this mutation enhances the activity of a specific DNA repair system. Which repair system is most likely affected by this mutation?
A researcher discovers a new mutation in a bacterial strain that increases its resistance to UV radiation. Further analysis reveals that this mutation enhances the activity of a specific DNA repair system. Which repair system is most likely affected by this mutation?
Flashcards
Direct Repair Mechanism
Direct Repair Mechanism
Repair processes that restore DNA to its wild-type state.
DNA Proofreading
DNA Proofreading
The ability of DNA polymerase to correct mismatched nucleotides during replication.
Photoreactive Repair
Photoreactive Repair
DNA repair mechanism using light to remove UV damage without excision.
Base Excision Repair (BER)
Base Excision Repair (BER)
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Nucleotide Excision Repair (NER)
Nucleotide Excision Repair (NER)
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Mismatch Repair
Mismatch Repair
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Xeroderma Pigmentosum (XP)
Xeroderma Pigmentosum (XP)
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UV-induced DNA Damage
UV-induced DNA Damage
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NER genes
NER genes
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Translesion DNA Synthesis
Translesion DNA Synthesis
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Double-Strand Breaks (DSB)
Double-Strand Breaks (DSB)
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Nonhomologous End Joining
Nonhomologous End Joining
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Synthesis-Dependent Strand Annealing
Synthesis-Dependent Strand Annealing
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DNA Damage-Signaling Systems
DNA Damage-Signaling Systems
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DNA damage response
DNA damage response
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DNA Mutation
DNA Mutation
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Intercalating Agents
Intercalating Agents
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Ionizing Radiation
Ionizing Radiation
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UV Radiation
UV Radiation
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DNA Repair Systems
DNA Repair Systems
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Spontaneous Changes
Spontaneous Changes
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Mechanisms of DNA Mutation
Mechanisms of DNA Mutation
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Redundancy in DNA Repair
Redundancy in DNA Repair
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Study Notes
Course Information
- Course name: HUBI 2004, Fundamentals of Modern Molecular Biology
- Instructor: Khadija Rebbani, PhD
- Date: January 27, 2025
- Textbook: Genetic Analysis: Integrated approach, 3rd edition, by Sanders & Bowman, Pearson's.
- Illustrations primarily from textbook, other sources cited below each illustration.
DNA Recombination, Mutations, and Repair
DNA Recombination
- A molecular process involving exchange of DNA fragments (genetic material) between:
- Multiple chromosomes (homologous or non-homologous)
- Different regions of the same chromosome.
- A natural process with variable occurrence among organisms.
- Tightly regulated but still stochastic in some aspects.
- Errors lead to diseases.
Learning Objectives (DNA Recombination)
- Understand DNA recombination's role in genetic diversity.
- Know the homologous recombination mechanism via the Holliday junction model.
- Identify homologous recombination errors and their effects.
Introduction (DNA Recombination)
- DNA's shared processes (replication and transcription) and similar genetic code across all living things suggest a single origin of life, evolving to millions of extant and extinct species.
- Life isn't static, it evolves as DNA diversifies.
DNA Recombination: Crossing Over
- The process of breakage and reunion of DNA fragments within homologous chromosomes, producing reciprocal recombination.
- A vital part of accurate chromosome segregation during mammalian meiosis.
DNA Recombination: Crossing Over (prophase I stages)
- Leptotene: Chromosomes condense.
- Zygotene: Homologous chromosomes pair.
- Pachytene: Synaptonemal complex forms; recombination nodules appear.
- Diplotene: Synaptonemal complex begins to dissolve, chiasmata (cross points) visible.
- Diakinesis: Chromosomes further condense, preparing for segregation.
Mechanisms of Crossing Over (Zygotene)
- Synapsis: Homologous chromosomes come into close contact and align.
- Synaptonemal complex: Trilayer protein bridge formed during synapsis, tightly binding non-sister chromatids.
Mechanisms of Crossing Over (Pachytene)
- Recombination nodules: Structures within the synaptonemal complex involved in the crossing over genetic material between nonsister chromatids.
- Crossing over involves exchange of genetic material between the non-sister chromatids.
Holliday Model
- A proposed model initially to describe meiotic recombination based on bacterial recombination studies.
- Steps in the model:
- Single-strand nicks formed on both DNA duplexes at identical positions.
- Strand invasion: Base pairing between nicked strands of the two duplexes.
- Branch migration: Holliday junction movement.
- Resolution: Holliday junction is cleaved, forming two separate DNA duplexes.
- Two resolutions: crossover (option A) or non-crossover (option B).
Updated Holliday Model
- The current "double-stranded break" model is more accurate than the Holliday model:
- Meiotic recombination is initiated by double-stranded DNA breaks.
- Recombination occurs in a programmed manner through specialized enzymes.
The Double-Stranded Break Model
- Key steps in the double-stranded break model of homologous recombination
- Double-stranded break created by Spo11 in one of the DNA duplexes.
- Mrx and Exo1 associate with Spo11, digesting the cut strands
The Double Stranded Break Model (continuation)
- Dmc1 and Rad51 join at trimmed regions, assembling strand-exchange nucleoprotein filaments.
- Strand invasion creates a D loop and the first heteroduplex region; Rad52, Rad59 and other proteins participate.
- Strand extension by DNA polymerase displaces D loop DNA, pairing with complementary single-stranded DNA in the other duplex, forming the second heteroduplex region.
- Double Holliday junctions form after nick sealing occurs; chromatids contain offset heteroduplexes.
- Resolution (A: opposite-sense; B: same-sense)
Errors in Crossing Over
- Inversion
- Unequal crossing over: Duplication or deletion of chromosomal segments.
- Translocation:
- Reciprocal balanced translocation: No genetic material loss.
- Reciprocal unbalanced translocation: Genetic material loss.
- Robertsonian translocation: Fusion of non-homologous chromosomes; likely loss of non-essential segments.
Mutations
- Heritable changes in DNA sequence of a cell.
- Key characteristics:
- Randomness: Equal probability of mutation at every base pair.
- Rarity: Extremely low average rates.
Classification of Mutations
- By cell type:
- Germline: Mutations in reproductive cells, heritable.
- Somatic: Mutations in non-reproductive cells, not heritable.
- By location in gene:
- Coding sequence: Changes in amino acid sequence.
- Regulatory mutations: Alteration in gene expression levels.
Point Mutations
- One or a few DNA base pairs are substituted, added or deleted at a particular location within a gene.
- Subtypes:
- Base-pair substitutions: Transitions or transversions.
- Indels: Insertion or deletion of base pairs.
Functional Impacts of Point Mutations
- Synonymous: No protein change; silent mutation.
- Missense: Amino acid change.
- Loss-of-function: Reduced or absent protein activity (amorphic-null or hypomorphic - leaky)
- Gain-of-function: Increased or new protein activity (hypermorphic-increased or neomorphic-new activity).
- Nonsense: Premature stop codon, truncated protein.
- Frameshift: Shifts the reading frame, changes amino acid sequence from the point of mutation to the end of the protein.
Causes of Mutations
- Spontaneous: Random errors in replication, or changes in chemical structure of nucleotide bases
- Agents:
- Chemical mutagens that directly interact with DNA (Nucleotide base analogs, Deaminating agents, Alkylating Agents, Hydroxylating Agents, DNA Intercalating agents)
- Physical mutagens (Ionizing radiation)
DNA Repair
- Mechanisms to counteract damage and maintain DNA integrity
- Categories: -Direct Repair: Repair happens directly without a template (e.g., Photoreactivation). -Indirect Repair: A template is utilized to fix the damage (e.g., Base excision repair, nucleotide excision repair, mismatch repair, or homologous recombination).
Key DNA Repair Mechanisms
- DNA Proofreading: DNA polymerase corrects errors during replication.
- Photoreactive repair: UV light-induced thymine dimers are repaired by photolyases
- Base excision repair (BER): Damaged/mismatched base is removed and replaced.
- Nucleotide excision repair (NER): Larger damaged sections of DNA are removed and replaced.
- Mismatch repair: Non-complementary base pairs that escape proofreading are repaired.
- Translesion DNA Synthesis (TLS): Allows replication to continue past DNA damage.
- Double-strand break repair:
- Nonhomologous end joining: Error-prone, directly joining broken ends
- Synthesis-dependent strand annealing: Error-free, utilizes undamaged sister chromatids for repair.
Other Important Aspects
- DNA damage-signaling systems: Crucial for recognizing damage, initiating repair processes.
Summary (Overall)
- DNA recombination, mutations, and DNA repair are essential aspects of molecular biology, maintaining genetic stability and variability, leading to the evolution of life.
- Mechanisms vary depending on the type of alteration or damage and involve specific proteins.
- Genetic disorders can arise from dysfunctional repair pathways.
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Description
Explore DNA recombination, a key molecular process for genetic diversity involving DNA fragment exchange between chromosomes. Understand the Holliday junction model and the consequences of errors in homologous recombination.
