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Questions and Answers
What is one consequence of strand slipping during DNA replication?
What is one consequence of strand slipping during DNA replication?
Which type of mutation is caused by deamination?
Which type of mutation is caused by deamination?
Which of the following correctly describes the role of intercalating agents?
Which of the following correctly describes the role of intercalating agents?
What type of repair mechanism specifically occurs during or immediately following DNA replication?
What type of repair mechanism specifically occurs during or immediately following DNA replication?
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How does UV radiation impact DNA?
How does UV radiation impact DNA?
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What is the primary consequence of defects in DNA repair mechanisms?
What is the primary consequence of defects in DNA repair mechanisms?
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Which of the following methods is NOT a type of excision repair?
Which of the following methods is NOT a type of excision repair?
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What type of mutation is caused by spontaneous events such as DNA tautomers or strand slipping?
What type of mutation is caused by spontaneous events such as DNA tautomers or strand slipping?
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What is the primary role of mobile genetic elements in the genome?
What is the primary role of mobile genetic elements in the genome?
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During DNA replication, what happens if unrepaired DNA damage is present?
During DNA replication, what happens if unrepaired DNA damage is present?
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Which of the following repair mechanisms is associated with addressing double-strand breaks?
Which of the following repair mechanisms is associated with addressing double-strand breaks?
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What ultimately leads to the development of cancer in relation to DNA?
What ultimately leads to the development of cancer in relation to DNA?
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What is the function of DNA damage repair mechanisms?
What is the function of DNA damage repair mechanisms?
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What is the main function of base excision repair?
What is the main function of base excision repair?
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Which repair mechanism involves excision nuclease and helicase?
Which repair mechanism involves excision nuclease and helicase?
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What genetic condition is associated with defects in nucleotide excision repair?
What genetic condition is associated with defects in nucleotide excision repair?
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What is a key consequence of unrepaired double strand breaks?
What is a key consequence of unrepaired double strand breaks?
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What is the primary characteristic of homologous recombination?
What is the primary characteristic of homologous recombination?
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Which process is primarily responsible for repairing mutations caused by ionizing radiation?
Which process is primarily responsible for repairing mutations caused by ionizing radiation?
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What kind of mobile genetic elements are transposons?
What kind of mobile genetic elements are transposons?
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Which enzyme is responsible for excising transposons in DNA transposons?
Which enzyme is responsible for excising transposons in DNA transposons?
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What type of transposon movement exists in retrotransposons?
What type of transposon movement exists in retrotransposons?
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What is the primary role of reverse transcriptase in retrotransposons?
What is the primary role of reverse transcriptase in retrotransposons?
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What is the primary result of base analogs on DNA during replication?
What is the primary result of base analogs on DNA during replication?
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Which element is primarily associated with the creation of pyrimidine dimers in DNA?
Which element is primarily associated with the creation of pyrimidine dimers in DNA?
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What distinguishes mismatch repair systems from other excision repair mechanisms?
What distinguishes mismatch repair systems from other excision repair mechanisms?
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What is a common characteristic of intercalating agents?
What is a common characteristic of intercalating agents?
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During the repair of DNA, what role does the translesion DNA polymerase play?
During the repair of DNA, what role does the translesion DNA polymerase play?
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What is the primary mechanism that addresses DNA damage caused by physical agents like UV radiation?
What is the primary mechanism that addresses DNA damage caused by physical agents like UV radiation?
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Which factor significantly influences the mutation rate in DNA?
Which factor significantly influences the mutation rate in DNA?
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What happens to DNA if defects in repair mechanisms are not addressed over time?
What happens to DNA if defects in repair mechanisms are not addressed over time?
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What is the role of mobile genetic elements concerning gene expression?
What is the role of mobile genetic elements concerning gene expression?
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Which type of DNA repair is involved specifically with mismatches during DNA replication?
Which type of DNA repair is involved specifically with mismatches during DNA replication?
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What is a common effect of chemical agents like base analogues on DNA?
What is a common effect of chemical agents like base analogues on DNA?
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Which DNA repair mechanism is preferred when repairing double-strand breaks in the presence of a homologous template?
Which DNA repair mechanism is preferred when repairing double-strand breaks in the presence of a homologous template?
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What role do mutagens play in relation to DNA?
What role do mutagens play in relation to DNA?
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What type of DNA damage does nucleotide excision repair specifically target?
What type of DNA damage does nucleotide excision repair specifically target?
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What is a major disadvantage of nonhomologous end joining (NHEJ) in the DNA repair process?
What is a major disadvantage of nonhomologous end joining (NHEJ) in the DNA repair process?
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Which repair mechanism involves the removal and replacement of abasic nucleotides?
Which repair mechanism involves the removal and replacement of abasic nucleotides?
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What defines homologous recombination compared to other repair mechanisms?
What defines homologous recombination compared to other repair mechanisms?
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What is the role of transposase in DNA transposons?
What is the role of transposase in DNA transposons?
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Which type of genetic element is primarily associated with reverse transcriptase?
Which type of genetic element is primarily associated with reverse transcriptase?
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What is one notable impact of defective nucleotide excision repair related to disease?
What is one notable impact of defective nucleotide excision repair related to disease?
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How do mobile genetic elements like transposons affect the genome?
How do mobile genetic elements like transposons affect the genome?
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Which of the following processes is a consequence of unrepaired double strand breaks?
Which of the following processes is a consequence of unrepaired double strand breaks?
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What type of DNA damage is likely to be repaired through base excision repair?
What type of DNA damage is likely to be repaired through base excision repair?
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Study Notes
DNA Repair and Recombination
- Lecture date: 9/14/2024
- Presenter: Tobias Weinrich, PhD
- Affiliation: School of Integrative Biological and Chemical Sciences, The University of Texas Rio Grande Valley
Learning Objectives
- Describe mechanisms ensuring accurate DNA replication
- Compare and contrast DNA damage types and excision repair methods
- Explain how DNA repair defects lead to cancer
- Summarize mechanisms for repairing double-strand breaks
- Explain mobile genetic elements, their transposition methods, and influence on gene expression
- Describe types of viruses and their genomes
Lecture Structure
- Fidelity of DNA replication
- DNA damage
- DNA repair mechanisms:
- Single-strand – excision repair
- Mismatch Repair
- Base excision repair
- Nucleotide excision repair
- Double-strand breaks
- Nonhomologous end joining (NHEJ)
- Homologous recombination
- Mobile genetic elements
- Transposons
- Retrotransposons
- Retroviruses
- Viruses (DNA or RNA genome)
- Viral morphologies
- Viral cycle
Mutation Rate and DNA Damage
- Mutation: Permanent nucleotide sequence change in DNA (positive/neutral/negative)
- Mutation rate = copying errors x unrepaired DNA damage
- DNA replication fidelity:
- Errors per nucleotide added during replication steps: -5'→ 3' polymerization: 1 in 105 -3'→ 5' exonucleolytic proofreading: 1 in 102 -Strand-directed mismatch repair: 1 in 103 -Combined error rate: 1 in 1010
- DNA damage:
- Spontaneous: DNA tautomers, strand slippage, damage to individual bases
- Induced by mutagens (physical and chemical):
- Physical: UV radiation, ionizing radiation
- Chemical: base analogues, base-modifying agents, intercalating agents
- Biological: mobile genetic elements
Defects in DNA Repair
- Accumulated unrepaired DNA events over time
- Defects in repair mechanisms lead to increased mutation accumulation, potentially causing cancer
Table 5-2: Inherited Human Syndromes
- Presents various human conditions related to DNA repair deficiencies and their corresponding phenotypes (e.g., colon cancer, skin cancer, UV sensitivity, neurological abnormalities)
DNA Damage - Spontaneous Mutations
- Tautomeric forms: Rare alternate resonance structures of nitrogenous bases cause base pair mismatches
- Strand Slipping: DNA polymerase may replicate a short DNA segment twice, especially regions with highly repetitive DNA
- Trinucleotide repeat disorders: Diseases associated with repeat expansions
- Specific diseases (fragile X syndrome, Friedrich ataxia, Huntington disease, myotonic dystrophy, spinal and bulbar muscular atrophy, spinocerebellar ataxia), their respective repeat sequences, and typical symptoms.
DNA Damage – Mutagens
- Base analogues: Resemble nitrogenous bases in structure, leading to different base pairings
- Base-modifying agents: Chemically alter DNA bases, creating adducts
- Intercalating agents: Intercalate between bases, distorting the local 3D shape of DNA
- Radiation:
- UV radiation: Causes pyrimidine dimers (covalent bonds between adjacent thymidines)
- Ionizing radiation: Removes electrons from biological molecules. Causes double-strand breaks.
Repair System
- Direct repair: Chemical reversion
- Excision repair systems:
- Mismatch repair: Occurs during or immediately after replication, distinguishing parental/newly synthesized strands
- Base excision repair
- Nucleotide excision repair
- Translesion DNA polymerase
- Light-dependent repair
- Pyrimidine dimers are primarily the target
Base Excision Repair
- DNA glycosylase removes base; AP endonuclease removes abasic nucleotide; Repair DNA Pol fills gap; DNA ligase seals the nick
Nucleotide Excision Repair
- Repair machinery recognizes DNA distortion; Excision nuclease cuts on each side; DNA helicase removes segment; Repair DNA polymerase fills gap; DNA ligase seals the nick
- Xeroderma pigmentosum: Defects in nucleotide excision repair leading to skin cancer
Double-Strand Repair
- Causes: Ionizing radiation, replication fork mishaps, strong oxidizing agents, metabolites (anticancer drugs)
- Repair mechanisms:
- Nonhomologous end joining (NHEJ): Predominant method, but may introduce mutations
- Homologous recombination: Flawless repair, no information loss
Nonhomologous End Joining (NHEJ)
- Repair process loses base pairs; introduces mutations by deletions
- Introns and most DNA being non-coding make this not as problematic as other types of damage
- Translocation – unlikely
Homologous Recombination
- Exchange of strands between separate DNA molecules, using the undamaged homologous chromosome as a template
- Flawless repair preserving genetic information
- BRCA-1/BRCA-2 defects linked to breast cancer risk
Replication Collapse in Homologous Recombination
- Replication collapse due to presence of "nicks" blocks DNA polymerase progress
Mobile Genetic Elements
- Transposons: Mobile genetic elements moving in a genome
- When moving, transposons can change gene order, generate new information, or moderately repeat in the genome -Allow for homologous recombination, being a mechanism for repair and evolution -Molecular parasites: Cells cannot get rid of them; no apparent function except for maintenance -Encode enzymes for movement, including transposase, integrase, and reverse transcriptase.
DNA Transposons and Retrotransposons
- DNA transposons: Conservative (cut and paste) & replicative (copy and paste) transposition mechanisms
- Retrotransposons: Copy and paste transposition mechanism, utilizing RNA intermediate and reverse transcriptase
Viruses – DNA or RNA genome
- Viruses: Small parasites replicating only in host cells; examples listed
- Viral genomes: DNA or RNA, single-stranded or double-stranded. Examples of viruses with each type are included in Table 6-2.
Viruses – Morphologies
- Naked, enveloped, helical, icosahedral, complex morphologies are presented in the visual aids; examples are given in the visual aids (e.g., T4 phage, bacterial virus, Potato virus X, Adenovirus, human+ virus, Influenza virus)
Viruses – Cycle
- Obligate cellular parasites: Rely on cell machinery to replicate
- Replication cycle (stages of viral replication) illustrated through a diagram, showing adsorption, endocytosis, fusion, replication, transcription, etc.
Retroviruses – RNA Genome
- Retroviruses integrate into host cells through DNA by recombination with reverse transcriptase; steps in retroviral replication are shown.
Mobile Genetic Elements – β-globin Cluster
- Shows location of Alu and L1 elements within the human β-globin cluster, highlighting their frequency in our genomes. Percentage of genome composition is given.
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Description
Test your understanding of DNA repair mechanisms and the role they play in preventing cancer. This quiz covers topics such as DNA damage types, excision repair methods, and mobile genetic elements discussed in the lecture. Assess your knowledge of the fidelity of DNA replication and the effects of mutations.
