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Questions and Answers
During which phase of the cell cycle does DNA replication occur?
During which phase of the cell cycle does DNA replication occur?
Microsatellite instability only involves the expansion of repetitive sequences.
Microsatellite instability only involves the expansion of repetitive sequences.
False
Name one type of structural chromosomal instability.
Name one type of structural chromosomal instability.
Deletion, amplification, inversion, or translocation
Which of the following is an example of a genotoxic agent?
Which of the following is an example of a genotoxic agent?
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Aneuploidy is a form of ______ instability.
Aneuploidy is a form of ______ instability.
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Match the instability type with its description:
Match the instability type with its description:
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Which of these best describes genomic instability?
Which of these best describes genomic instability?
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A normal MMR system in microsatellites will lead to expansion of repeats
A normal MMR system in microsatellites will lead to expansion of repeats
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Which of the following is an example of an exogenous genotoxic agent?
Which of the following is an example of an exogenous genotoxic agent?
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Base methylation is an example of an endogenous genotoxic agent.
Base methylation is an example of an endogenous genotoxic agent.
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What is the result of AFB1, 8, 9-exo-epoxide interacting with DNA?
What is the result of AFB1, 8, 9-exo-epoxide interacting with DNA?
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The hydrolysis process of DNA leading to the removal of a purine base is known as base ______.
The hydrolysis process of DNA leading to the removal of a purine base is known as base ______.
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Match the following DNA damage response steps with their descriptions:
Match the following DNA damage response steps with their descriptions:
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Which of the following is NOT a direct effect of ionizing radiation (IR) on DNA?
Which of the following is NOT a direct effect of ionizing radiation (IR) on DNA?
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Mitotic defects can contribute to genome instability leading to abnormal chromosome segregation.
Mitotic defects can contribute to genome instability leading to abnormal chromosome segregation.
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Name two types of DNA crosslinks that can occur as forms of DNA damage.
Name two types of DNA crosslinks that can occur as forms of DNA damage.
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Which of the following describes the correct sequence of the DNA damage response?
Which of the following describes the correct sequence of the DNA damage response?
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Nonhomologous end joining (NHEJ) is a DNA repair pathway that uses a homologous template.
Nonhomologous end joining (NHEJ) is a DNA repair pathway that uses a homologous template.
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What does ATM stand for?
What does ATM stand for?
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The protein complex that loads onto the DNA during replication licensing is called the ______ complex.
The protein complex that loads onto the DNA during replication licensing is called the ______ complex.
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Match the following DNA repair mechanisms with their descriptions:
Match the following DNA repair mechanisms with their descriptions:
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Which of the following is NOT a factor leading to genome instability?
Which of the following is NOT a factor leading to genome instability?
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Re-replication is an event that occurs when the DNA experiences a timely initiation.
Re-replication is an event that occurs when the DNA experiences a timely initiation.
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Name three unusual DNA structures that can interfere with replication.
Name three unusual DNA structures that can interfere with replication.
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During which phase of mitosis does the mitotic checkpoint occur?
During which phase of mitosis does the mitotic checkpoint occur?
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DNA methylation patterns are not related to genomic stability.
DNA methylation patterns are not related to genomic stability.
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What is insertional mutagenesis, and how is it related to DNA hypomethylation?
What is insertional mutagenesis, and how is it related to DNA hypomethylation?
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The process of rearranging nucleosomes to alter chromatin structure is called ______ remodeling.
The process of rearranging nucleosomes to alter chromatin structure is called ______ remodeling.
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Match the following epigenetic mechanisms with their functions.
Match the following epigenetic mechanisms with their functions.
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Which of the following is NOT associated with hypermethylation?
Which of the following is NOT associated with hypermethylation?
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Histone acetylation typically leads to a more open chromatin structure.
Histone acetylation typically leads to a more open chromatin structure.
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Describe the three stages involved in nucleosome assembly?
Describe the three stages involved in nucleosome assembly?
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Which of the following best describes the role of telomerase?
Which of the following best describes the role of telomerase?
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Centromeric non-coding RNAs play a role in regulating telomere length.
Centromeric non-coding RNAs play a role in regulating telomere length.
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Name one class of transposable element that uses an RNA intermediate during its transposition.
Name one class of transposable element that uses an RNA intermediate during its transposition.
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The modification of histones with H3K9me2/3 is often coupled with ______ methylation.
The modification of histones with H3K9me2/3 is often coupled with ______ methylation.
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Match the following terms related to telomeres with their descriptions:
Match the following terms related to telomeres with their descriptions:
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Which histone modification is associated with DNA double-strand break repair?
Which histone modification is associated with DNA double-strand break repair?
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The SWI/SNF complex plays a role in regulating DNA repair pathways.
The SWI/SNF complex plays a role in regulating DNA repair pathways.
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Name one common type of epigenetic modification that influences the choice between NHEJ and HR DNA repair pathways.
Name one common type of epigenetic modification that influences the choice between NHEJ and HR DNA repair pathways.
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The protein ____ is a component of the centromere and is involved in kinetochore formation.
The protein ____ is a component of the centromere and is involved in kinetochore formation.
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What can create a replisome obstacle?
What can create a replisome obstacle?
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Match the following terms with their descriptions:
Match the following terms with their descriptions:
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Misregulation of centromere function can lead to chromosomal instability.
Misregulation of centromere function can lead to chromosomal instability.
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What is the primary function of chromatin remodelers concerning stalled replication forks?
What is the primary function of chromatin remodelers concerning stalled replication forks?
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Study Notes
Course Information
- Course Title: Applied Genetics and Epigenetics
- Course Number: GNSA 503
- University: Lebanese University, R. Hariri University Campus
- Faculty: Sciences Faculty/EDST
- Department: Biology/Biochemistry Department
- Academic Year: 2024-2025
- Office: 2-45
- Level: Master 2R: GNSA
Genome Stability
- Definition: Genomic instability is a state where there's a heightened tendency to acquire inheritable genetic alterations affecting the phenotype.
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Levels of Genomic Instability:
- Numerical CIN: Includes aneuploidy (abnormal number of chromosomes).
- Structural CIN: Includes duplications, inversions, and translocations of chromosome segments.
- Genome Instability: Includes microsatellite instability and nucleotide instability.
- Microsatellite Instability: Refers to errors in the repetitive sequences (microsatellites) in the genome.
- Nucleotide Instability: Involves errors in single nucleotide bases.
Cell Cycle
- Stages: Includes mitosis and cytokinesis; cell cycle stages (G1, S, G2, M).
- Regulation: Cell cycle checkpoints monitor for DNA damage during certain phases; cyclin-dependent kinases (CDKs) regulate the cell cycle.
- DNA damage response: The cell cycle can halt at various phases to repair DNA damage, or if damage is extensive, initiate apoptosis.
Factors Causing Genome Instability
- External Factors: Includes genotoxic agents (e.g., UV radiation, ionizing radiation, toxins, alkylating agents).
- Internal Factors: Includes endogenous chemicals (reactive oxygen species (ROS)), replication defects, cell cycle defects, and epigenetic alterations.
- Genotoxic agents: Endogenous (generated within the body) and exogenous (from outside the body) agents cause DNA damage.
- Types of DNA damage: Base depurination/deamination, base oxidation, base methylation, single-strand breaks, double-strand breaks, cross-links, and mismatch bases.
- Specific Mechanisms: Such as DNA repair defects (failure of mechanisms to repair damaged DNA) leading to ongoing accumulation of DNA damage.
ATM/ATR Signaling Network
- DNA Damage Recognition: Proteins like Mre11 complex detect DNA damage (DSBs and SSBs).
- Signal Transduction: Activation of proteins like ATM or ATR, leading to signal amplification and cellular response.
- Cellular Decisions: Activation of p53, triggering cell cycle arrest, DNA repair, or apoptosis.
DNA Damage Response Pathways
- Base Excision Repair (BER): Repairs single base damages.
- Nucleotide Excision Repair (NER): Repairs bulky DNA lesions.
- Mismatch Repair (MMR): Corrects DNA replication errors.
- Homologous recombination (HR): A DNA repair pathway that utilizes homologous DNA sequences to repair double-strand breaks.
- Non-homologous end joining (NHEJ): A DNA repair pathway that directly joins the ends of double-strand breaks without requiring a homologous template.
Internal Factors Causing Genome Instability
- Replication Dysfunction: Includes issues with initiation density, untimely initiation causing re-replication, and fork reversal, impacting DNA replication fidelity.
- Transcription-Replication Collisions: Transcription and replication processes clashing, resulting in DNA damage.
- Unusual DNA Structures: Formation of DNA structures that cannot be readily replicated or repaired, such as G-quadruplexes and R-loops.
- Mitotic Defects: Problems in proper chromosome segregation during mitosis, leading to aneuploidy.
Epigenetic Regulation
- DNA Methylation: A chemical modification crucial in gene regulation, can affect the expression (turning on/off) of genes that lead to genomic instability.
- Nucleosome Remodeling: Process that changes the packing and accessibility of DNA, impacting gene expression.
- Histone Modifications: Alteration of histone proteins, impacting the structure of the chromatin and gene expression.
- Noncoding RNAs: Functional RNA molecules not translated into proteins, affecting gene regulation.
DNA Methylation, Genomic Instability
- Hypomethylation and hypermethylation can lead to aberrant gene expression and genomic instability.
- Hypomethylation often promotes oncogene expression, while hypermethylation often suppresses tumor suppressor gene expression.
Epigenetic Control of Centromeres
- Important for chromosome segregation.
- CENP-A plays a key role in centromere development and cell division.
Epigenetic Control of Telomeres
- Telomere maintenance: Loss of telomere protection due to shortening or disruption can lead to genomic instability.
- HP1a can enhance telomere heterochromatin formation.
Epigenetic Control of Transposable Elements
- Transposable elements (TEs) can cause genomic instability if not regulated properly.
- Methylation of TEs can silence their activity and inhibit mobility.
- Histone modifications can also silence TEs and stop them from disrupting genes.
Epigenetic Modification in DNA Repair
- Epigenetic mechanisms (chromatin remodeling, DNA methylation, etc.) significantly impact the efficiency of DNA repair pathways and the selection of repair pathways.
Epigenetic Modification in DNA Replication
- Epigenetic modifications are related to DNA replication stress, for example, chromatin remodeling at stalled replication forks and heterochromatin assembly.
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Description
Test your knowledge on genomic instability, DNA replication, and the various agents that can cause DNA damage. This quiz covers key concepts related to the cell cycle, types of chromosomal instability, and examples of genotoxic agents. Enhance your understanding of crucial molecular biology topics.
