Podcast
Questions and Answers
What is the consequence of a mutation occurring in germ-line cells?
What is the consequence of a mutation occurring in germ-line cells?
Which of the following is NOT a consequence of DNA damage if not repaired in time?
Which of the following is NOT a consequence of DNA damage if not repaired in time?
What role does the proofreading system play in DNA replication?
What role does the proofreading system play in DNA replication?
Which type of mutation arises from environmental damaging agents?
Which type of mutation arises from environmental damaging agents?
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What is one of the main damaging effects of high-energy ionizing radiation on DNA?
What is one of the main damaging effects of high-energy ionizing radiation on DNA?
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What type of DNA damage does nucleotide excision repair primarily address?
What type of DNA damage does nucleotide excision repair primarily address?
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Which organism utilizes UvrABC excinuclease for the nucleotide excision repair process?
Which organism utilizes UvrABC excinuclease for the nucleotide excision repair process?
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What is a consequence of defects in nucleotide excision repair in humans?
What is a consequence of defects in nucleotide excision repair in humans?
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What role does the methylation of GATC sequences serve in mismatch repair in E. coli?
What role does the methylation of GATC sequences serve in mismatch repair in E. coli?
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Which step is NOT part of the nucleotide excision repair process?
Which step is NOT part of the nucleotide excision repair process?
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The repair of pyrimidine dimers in eukaryotes involves which of the following?
The repair of pyrimidine dimers in eukaryotes involves which of the following?
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What type of DNA damage results from UV radiation exposure?
What type of DNA damage results from UV radiation exposure?
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What is the first step in the excision repair systems for DNA?
What is the first step in the excision repair systems for DNA?
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What type of damage does base excision repair primarily correct?
What type of damage does base excision repair primarily correct?
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What is the role of DNA glycosylases in base excision repair?
What is the role of DNA glycosylases in base excision repair?
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Which of the following represents a type of genetic damage that base excision repair can fix?
Which of the following represents a type of genetic damage that base excision repair can fix?
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Which statement regarding proofreading systems during DNA replication is correct?
Which statement regarding proofreading systems during DNA replication is correct?
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What happens after the DNA glycosylases remove abnormal bases in base excision repair?
What happens after the DNA glycosylases remove abnormal bases in base excision repair?
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Which environmental factor is associated with the deamination process affecting DNA bases?
Which environmental factor is associated with the deamination process affecting DNA bases?
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What occurs after the DNA polymerase I synthesizes a new piece of DNA in the base excision repair process?
What occurs after the DNA polymerase I synthesizes a new piece of DNA in the base excision repair process?
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Study Notes
DNA Damage and Repair
- DNA sequence is highly protected from harm because each cell contains only one or two copies of its DNA
- DNA is a relatively stable molecule, but Earth's natural environment is toxic. Damage to DNA is inevitable and can also be altered by mistakes during replication or recombination
- Damage and sequence alterations to DNA are often quickly repaired, but if left unrepaired, result in a permanent alteration and harbor mutations.
- Mutations are changes in DNA sequence. When mutations occur in germ-line cells, these changes are inheritable.
- Cancer cells have mutations that prevent cell death, leading to uncontrolled cell division and malignant tumors that can harm the entire organism.
- Cells have limited time to fix initial alterations before replication converts the alteration into a mutation passed down to the next generation
- Somatic mutations occur in somatic cells and only affect the individual in which the mutation arises.
- Germ-line mutations alter gametes, and are passed to the next generation.
- Errors can occur during DNA replication, with an error occurring for every 30,000 bases and despite the proofreading system.
- Environmental insults are damaging agents.
- Maintenance of the integrity of DNA molecules is vital for the survival of species/organisms.
Types of DNA Damage
- Damaging agents can be either chemicals (e.g., nitrous acid, which deaminates bases), or radiation (e.g., non-ionizing UV radiation fusing pyrimidines or high-energy ionizing radiation like X-rays that cause double-strand breaks)
- Bases are also spontaneously altered or lost in mammalian DNA at a high rate (thousands per cell per day).
- Radiations: Highly reactive oxygen radicals produced during normal cellular respiration and other biochemical pathways. Ionizing radiation includes gamma rays and X-rays. Ultraviolet rays, specifically UV-C (~260nm), absorb strongly by DNA. UV-B penetrates the ozone shield.
- Chemicals in the environment: Aromatic hydrocarbons (found in cigarette smoke), plant and microbial products (e.g., aflatoxin in moldy peanuts), and chemicals in chemotherapy (especially cancer chemotherapy).
Types of DNA Damage (examples)
| S.No. | Type of Damage | Examples |
|---|---|---|
| 1 | Single-base alteration | Depurination, Deamination of cytosine to uracil, Deamination of adenine to hypoxanthine, Alkylation of base, Insertion or deletion of nucleotide, Base-analog incorporation |
| 2 | Two-base alterations | UV light-induced thymine-thymine (pyrimidine) dimer |
| 3 | Chain breaks | Ionizing radiation, Radioactive disintegration of backbone element, Oxidative free radical formation |
| 4 | Cross-linkage | Between bases in the same or opposite strands; Between DNA and protein molecules (e.g., histones) |
DNA Damage Repair Overview
- Cells are remarkably efficient at repairing damage, especially to single or double bases on the same strand.
- Damage to both strands requires different repair systems.
- Most excision repair systems:
- Recognize the damage (lesion) on DNA
- Remove the damage
- Fill the gap using the undamaged complementary strand as a template for DNA synthesis
- Ligation to restore the continuity of the repaired strand
Types of DNA Repair
- Base excision repair (BER)
- Abnormal bases are removed by DNA glycosylases breaking the bond between the base and deoxyribose sugar of the DNA backbone.
- This leaves an empty space known as an AP-site.
- Nucleotide excision repair (NER)
- Recognizes bulky lesions that block DNA replication, like UV-induced pyrimidine dimers, common distortions in the helix, and incision on both sides of the lesion.
- Excises a short patch of DNA and repairs it by repolymerization and ligation.
- In E. coli, mediated by UvrABC excinuclease
- Defects in NER underlie Xeroderma pigmentosum (XP), a rare genetic disease where skin cells cannot repair pyrimidine dimers from sunlight resulting in extensive mutations and skin cancers.
- Mismatch repair
- Repairs replication errors that escape the proofreading activity (e.g., mismatch of bases).
- In E. coli, mediated by Mut proteins in two steps: identifying the incorrect strand and repairing the region
- Double-strand break repair (including NHEJ and homologous recombination)
- NHEJ: Direct joining of broken ends. Essential for NHEJ is a protein called Ku. Errors can cause translocations associated with cancers. - Example cancers: Burkitt's lymphoma, Chronic myelogenous leukemia (CML), B-cell leukemia
- Homologous Recombination: between homologous chromosomes. No loss of DNA as homologous chromosomes are used as a template to replace lost bases - Occurs during late S-phase or in G2 phase to repair complete breaks - Genes BRCA1 and BRCA2 are involved and mutations can predispose women to breast and ovarian cancers.
Summary of Repair mechanisms by type of DNA Damage
- Base excision repair (BER) corrects various base modifications.
- Nucleotide excision repair (NER) mainly repairs bulky damage.
- Mismatch repair (MMR) specifically targets mismatched bases in newly synthesised DNA strands . Double strand breaks (DSBs) are repaired by NHEJ or homologous recombination (HR) pathways.
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Description
Test your knowledge on DNA damage, repair mechanisms, and the implications of mutations in both somatic and germ-line cells. This quiz covers the essential concepts related to how DNA is protected and the consequences of its alterations. Perfect for biology students interested in genetics and cancer biology.
