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Questions and Answers
Which type of chemical mutagen would most likely cause the addition of a hydroxyl group to a nucleotide?
Which type of chemical mutagen would most likely cause the addition of a hydroxyl group to a nucleotide?
What is the primary purpose of the Ames Test?
What is the primary purpose of the Ames Test?
What kind of damage can ionizing radiation cause to DNA?
What kind of damage can ionizing radiation cause to DNA?
Which type of repair mechanism directly recognizes and reverses changes in DNA?
Which type of repair mechanism directly recognizes and reverses changes in DNA?
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What is the result of the formation of pyrimidine dimers in DNA?
What is the result of the formation of pyrimidine dimers in DNA?
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Which of the following is NOT true about alkylating agents?
Which of the following is NOT true about alkylating agents?
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Which of the following statements correctly characterizes chemical mutagens?
Which of the following statements correctly characterizes chemical mutagens?
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What happens during mismatch repair in DNA?
What happens during mismatch repair in DNA?
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Which type of radiation is responsible for producing ionizing effects on biological tissues?
Which type of radiation is responsible for producing ionizing effects on biological tissues?
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What is the role of liver enzymes in the Ames Test?
What is the role of liver enzymes in the Ames Test?
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What primarily causes spontaneous mutations in cells?
What primarily causes spontaneous mutations in cells?
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What is the role of DNA polymerases during DNA replication?
What is the role of DNA polymerases during DNA replication?
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Which of the following describes a tautomer and its effect on DNA?
Which of the following describes a tautomer and its effect on DNA?
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How do chemical mutagens typically affect DNA?
How do chemical mutagens typically affect DNA?
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What is the significance of genomic regions with repeat sequences concerning DNA replication errors?
What is the significance of genomic regions with repeat sequences concerning DNA replication errors?
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What does the Ames test commonly assess?
What does the Ames test commonly assess?
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How does radiation typically impact DNA?
How does radiation typically impact DNA?
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What occurs during strand slippage in DNA replication?
What occurs during strand slippage in DNA replication?
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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 enzyme is responsible for sealing the gap after DNA polymerase has filled it during mismatch repair?
Which enzyme is responsible for sealing the gap after DNA polymerase has filled it during mismatch repair?
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What is the primary cause of sickle shape in red blood cells for individuals with sickle-cell disease?
What is the primary cause of sickle shape in red blood cells for individuals with sickle-cell disease?
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In nucleotide excision repair, which protein cleaves the phosphodiester bonds on both sides of the DNA damage?
In nucleotide excision repair, which protein cleaves the phosphodiester bonds on both sides of the DNA damage?
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Which type of DNA repair is characterized by direct repair of pyrimidine dimers using visible light?
Which type of DNA repair is characterized by direct repair of pyrimidine dimers using visible light?
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What mutation type causes sickle-cell disease?
What mutation type causes sickle-cell disease?
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What is the primary consequence of DNA replication bypassing damaged sections?
What is the primary consequence of DNA replication bypassing damaged sections?
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What role does recombination repair serve in post-replication scenarios?
What role does recombination repair serve in post-replication scenarios?
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Which populations have higher frequencies of the bS allele, responsible for sickle-cell disease?
Which populations have higher frequencies of the bS allele, responsible for sickle-cell disease?
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Which enzyme is specifically involved in unwinding DNA during nucleotide excision repair?
Which enzyme is specifically involved in unwinding DNA during nucleotide excision repair?
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What is the initial step in mismatch repair when an error is detected?
What is the initial step in mismatch repair when an error is detected?
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What ultimately leads to chronic anemia in patients with sickle-cell disease?
What ultimately leads to chronic anemia in patients with sickle-cell disease?
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What is the genetic composition of individuals who are most favored in environments where malaria is endemic?
What is the genetic composition of individuals who are most favored in environments where malaria is endemic?
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Which mechanism leads to high frequencies of both normal and mutant alleles in a population?
Which mechanism leads to high frequencies of both normal and mutant alleles in a population?
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What is a likely outcome for individuals with homozygous conditions concerning malaria?
What is a likely outcome for individuals with homozygous conditions concerning malaria?
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How does the RBC lifespan of heterozygotes impact the malaria parasite's lifecycle?
How does the RBC lifespan of heterozygotes impact the malaria parasite's lifecycle?
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What evidence supports the heterozygote advantage in malaria-endemic areas?
What evidence supports the heterozygote advantage in malaria-endemic areas?
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What is a primary disadvantage of homozygosity compared to heterozygosity in terms of genetic fitness?
What is a primary disadvantage of homozygosity compared to heterozygosity in terms of genetic fitness?
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In regions where malaria is common, which of the following genotypes is least likely to survive and reproduce effectively?
In regions where malaria is common, which of the following genotypes is least likely to survive and reproduce effectively?
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What is one of the consequences of balancing selection on population genetic diversity?
What is one of the consequences of balancing selection on population genetic diversity?
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What primarily contributes to the background mutation rate among species?
What primarily contributes to the background mutation rate among species?
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What mechanism explains the alteration in the number of DNA repeats during replication?
What mechanism explains the alteration in the number of DNA repeats during replication?
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Which type of replication error is most frequently associated with spontaneous nucleotide base changes?
Which type of replication error is most frequently associated with spontaneous nucleotide base changes?
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What distinguishes induced mutations from spontaneous mutations?
What distinguishes induced mutations from spontaneous mutations?
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What best describes the role of DNA polymerases during DNA replication?
What best describes the role of DNA polymerases during DNA replication?
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Which chemical modifications can chemical mutagens induce in DNA?
Which chemical modifications can chemical mutagens induce in DNA?
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What happens during the process of strand slippage in DNA replication?
What happens during the process of strand slippage in DNA replication?
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What type of DNA change occurs as a result of tautomeric shifts during replication?
What type of DNA change occurs as a result of tautomeric shifts during replication?
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What type of chemical agent removes amino groups from nucleotides?
What type of chemical agent removes amino groups from nucleotides?
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What is a primary characteristic of intercalating agents?
What is a primary characteristic of intercalating agents?
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In the Ames Test, what does a significant increase in revertants indicate?
In the Ames Test, what does a significant increase in revertants indicate?
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Which repair mechanism is responsible for correcting errors that occur after DNA polymerase proofreading?
Which repair mechanism is responsible for correcting errors that occur after DNA polymerase proofreading?
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Which of the following best describes the effect of UV light on DNA?
Which of the following best describes the effect of UV light on DNA?
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Which type of radiation is characterized by high energy and short wavelength that can penetrate deeply into tissues?
Which type of radiation is characterized by high energy and short wavelength that can penetrate deeply into tissues?
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Which of the following methods directly repairs pyrimidine dimers found in DNA?
Which of the following methods directly repairs pyrimidine dimers found in DNA?
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What kind of damage is primarily caused by the use of alkylating agents?
What kind of damage is primarily caused by the use of alkylating agents?
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What is the main purpose of DNA repair systems in organisms?
What is the main purpose of DNA repair systems in organisms?
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What is the correct sequence of steps involved in mismatch repair?
What is the correct sequence of steps involved in mismatch repair?
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Which statement about photoreactivation repair is true?
Which statement about photoreactivation repair is true?
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In base excision repair, what is the function of DNA glycosylases?
In base excision repair, what is the function of DNA glycosylases?
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What characterizes nucleotide excision repair?
What characterizes nucleotide excision repair?
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In post-replication repair, what is the purpose of recombination repair?
In post-replication repair, what is the purpose of recombination repair?
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Which type of mutation leads to sickle-cell disease?
Which type of mutation leads to sickle-cell disease?
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What determines the sickle shape of red blood cells in sickle-cell disease?
What determines the sickle shape of red blood cells in sickle-cell disease?
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Which population is likely to show high frequencies of the bS allele?
Which population is likely to show high frequencies of the bS allele?
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What component ultimately leads to chronic anemia in patients with sickle-cell disease?
What component ultimately leads to chronic anemia in patients with sickle-cell disease?
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What is the role of UVR-C in nucleotide excision repair?
What is the role of UVR-C in nucleotide excision repair?
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What is the function of DNA ligase in the DNA repair mechanisms discussed?
What is the function of DNA ligase in the DNA repair mechanisms discussed?
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What are the primary components of the tetrameric structure of hemoglobin?
What are the primary components of the tetrameric structure of hemoglobin?
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Which amino acid substitution occurs in individuals with sickle-cell disease?
Which amino acid substitution occurs in individuals with sickle-cell disease?
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What type of genetic inheritance pattern is sickle-cell disease characterized by?
What type of genetic inheritance pattern is sickle-cell disease characterized by?
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Study Notes
Chemical Mutagens
- Chemical mutagens are classified by how they modify DNA
- Mismatch repair, photoreactivation repair, base excision repair, nucleotide excision repair & post-replication repair are examples of repair systems that correct DNA damage
Mismatch Repair
- In mismatch repair a nicked strand of DNA is removed with an endonuclease then replaced with a base filled in by polymerase and sealed by ligase
Photoreactivation Repair
- Photoreactivation repair fixes the bonds from UV exposure between pyrimidine dimers, which are broken by the enzyme photolyase using visible light energy
Base Excision Repair
- DNA glycosylases remove mispaired nucleotides in base excision repair, leaving an apurinic or apyrimidinic (AP) site which is then removed by AP endonuclease
Nucleotide Excision Repair
- Nucleotide excision repair breaks the phosphodiester bonds on the damaged DNA strand using UVR-A, UVR-B, and UVR-C proteins, then the damaged segment is released by helicase and repaired by DNA polymerase & ligase
Post-replication repair
- Recombination repair is the process that takes place during post-replication repair to fix large-scale DNA damage, where the incomplete segment is recombined with the complementary strand of the sister chromatid
Sickle-cell Disease
- Sickle-cell disease (SCD) is inherited disorder caused by a single base-pair substitution in the b-globin gene that changes an amino acid
- SCD patients are homozygous for the b S allele, have genotype b S/b S and experience pain and tissue damage from reduced blood flow due to sickle-shaped blood cells
- SCD is caused by an abnormal hemoglobin that causes the red blood cells to deform into a sickle shape
Sickle-cell Disease and Hemoglobin
- Hemoglobin molecules are tetramers with two a-globin and two b-globin chains, this arrangement is called hemoglobin A (HbA)
- The a-globin gene encodes a protein 141 amino acids long and b-globin encodes one 146 amino acids in length
- The mutant allele in SCD is called b S and the normal allele is called b A
- Heterozygous individuals carrying the sickle-cell allele have genotype b A/b S and are carriers of SCD
Sickle-cell Disease in Human Populations
- The S allele is found in frequencies up to 15% in several populations of Africa, the Middle East, India, and Madagascar
Chemical Mutagens
- Chemical mutagens modify DNA in specific ways to cause particular types of sequence changes
- Chemical mutagens can be classified by how they modify DNA
Types of Chemical Mutagens
- Nucleotide base analogs: have a similar structure to DNA nucleotides
- Deaminating agents: remove amino groups from nucleotides
- Alkylating agents: add side groups such as methyl (CH3) and ethyl (CH3-CH2) to nucleotides
- Oxidizing agents: add oxygen or remove hydrogen atoms from nucleotides
- Hydroxylating agents: add a hydroxyl group to the nucleotide
- Intercalating agents: insert between DNA base pairs
The Ames Test
- Mimics what happens when animals are exposed to chemicals
- Tests chemicals and their breakdown products for mutagenic potential
- Uses Salmonella typhimurium bacteria
- Bacteria are exposed to experimental compounds in the presence of mammalian liver enzymes
- In animals, ingested chemicals are transported to the liver, where they are broken down by enzymes
Ames Test Procedure
- Bacterial strains carry mutations that interfere with their ability to synthesize histidine (his-)
- Bacteria are exposed to the chemical to be tested, plus liver enzymes, and plated on a medium lacking histidine
- A chemical is mutagenic if there is a significant increase in the reversion rate in treated strains relative to controls
- The number of revertants from his- to his+ are assayed for each treatment or control
Electromagnetic Spectrum
- Includes ionizing radiation like gamma rays and X-rays and non-ionizing radiation like UV, infrared (IR), microwaves, and radio waves
- Ionizing radiation has short wavelengths and high energy
- Non-ionizing radiation has longer wavelengths and lower energy
- Wavelengths are measured in meters (m)
UV Light
- In UV light, pyrimidine dimers are produced by the formation of one or two additional covalent bonds between adjacent pyrimidine nucleotides
Ionizing Radiation
- Includes X-rays, gamma rays, and cosmic rays
- Short wavelengths, high energy and can penetrate deeply into tissues
- Can cause widespread damage and double-stranded breaks, which can lead to chromosomal aberrations
- Increases risk of leukemia and other cancers
Repair Systems
- Organisms preserve the fidelity of DNA using repair systems
- These systems either directly repair DNA damage or allow the organism to circumvent the problems caused by unrepaired damage
DNA Damage Repair Mechanisms
- Proofreading: The most direct way to repair DNA damage, done by DNA polymerase
- Mismatch repair: Corrects errors after proofreading
- Photoreactivation repair: Repairs pyrimidine dimers due to UV exposure in some bacteria/eukaryotes
- Base excision repair: Corrects mispairings due to chemical modification of bases
- Nucleotide excision repair: Excises and replaces UV-induced damage
- Post-replication repair: Repairs large-scale DNA damage that overwhelms other repair systems
Mismatch Repair
- Takes place in several steps:
- Endonuclease nicks the new strand with the error
- Exonuclease removes bases on the nicked strand
- DNA polymerase synthesizes to fill the gap
- DNA ligase seals the gap
Photoreactivation Repair
- The enzyme photolyase uses visible (blue) light to break the bonds between pyrimidine dimers
Base Excision Repair
- DNA glycosylases recognize and remove mispaired nucleotides
- AP endonuclease removes the remaining nucleotides
- DNA polymerase and DNA ligase fill and seal the gap
Nucleotide Excision Repair
- Two UVR-A proteins and one UVR-B bind the DNA strand opposite the damage
- UVR-A proteins dissociate
- One UVR-C joins UVR-B and cleaves phosphodiester bonds
- UVR-D unwinds DNA to release the damaged segment
- DNA polymerase synthesizes the missing nucleotides and DNA ligase seals the gap
Post-replication Repair
- DNA replication can bypass damaged sections, leaving single-stranded gaps
- Recombination repair uses the sister chromatid as a template to repair the incomplete segment
Sickle-Cell Disease (SCD)
- A potentially fatal, autosomal recessive disorder caused by a structural abnormality in hemoglobin (Hb)
- Affects the ability of Hb to carry oxygen
- Patients experience muscle pain when sickled blood cells impede blood flow in small vessels
- Sickled RBCs are removed from circulation, causing chronic anemia
Hemoglobin Structure
- Hemoglobin molecules are tetramers with two protein chains each of two different globin genes: a-globin and b-globin
- This arrangement is the most common form and is called hemoglobin A (HbA)
- Each of the four proteins carries one iron-containing molecule of heme, which reversibly binds to oxygen
The Globin Genes
- The a-globin and b-globin genes are organized similarly with three exons and two introns
- The a-globin gene encodes a protein 141 amino acids long and b-globin encodes one 146 amino acids in length
Sickle-Cell Disease
- Caused by a single base-pair substitution in the b-globin gene
- This changes an amino acid in the protein
- The mutant allele is called bS and the normal allele is called bA
- Individuals with SCD carry two bS alleles (Genotype bS/bS)
Cause of Sickle Shape in Red Blood Cells
- Two abnormal b-globin proteins joining two normal a-globin proteins create abnormal hemoglobin molecules
- These molecules collapse into linear, crystal-like molecules, causing red blood cells to deform
Heterozygous Individuals
- Heterozygous individuals (carriers of SCD allele) have genotype bA/bS
- Some of their hemoglobin molecules carry defective b-globin proteins
- They don't develop severe anemia, but are sometimes identified as having the sickle cell trait
Sickle-Cell Disease in Human Populations
- Dozens of variant alleles of hemoglobin genes produce various forms of hereditary anemia
- The S allele is found in frequencies up to 15% in several populations of Africa, the Middle East, India, and Madagascar.
Malaria As an Agent of Natural Selection
- An environment where malaria is endemic favors individuals who are heterozygous for A and one of the mutant alleles
- Malaria, caused by the parasite Plasmodium falciparum carried by the mosquito Anopheles gambeii, results in high fevers and can cause death
- Individuals with the genotype A/A succumb more easily to malaria or HbA/ HbA
- Those with genotype bS/ bS suffer from hereditary anemia
- Heterozygotes with genotype A/S survive and reproduce better in regions where malaria is common
Malaria As an Agent of Natural Selection
- The shorter lifespan of their RBCs thwarts the malaria parasite by interrupting the developmental cycle of Plasmodium
Heterozygote Advantage and Equilibrium Frequency
- Heterozygote advantage leads to a gene pool with high frequencies of both normal and mutant alleles
- The advantage is balanced by the disadvantages of homozygosity for either allele
- Conflicting pressures lead to equilibrium frequencies of normal and mutant alleles in the population
Evidence for Heterozygote Advantage
- The frequency of SCD carriers rises with increasing age in a population, due to earlier death of homozygotes
- Heterozygous women produce larger numbers of children on average
- Across the “malaria belt” the S allele has arisen and evolved independently at least three times
Gene Mutations May Arise Spontaneously
- Spontaneous mutations arise in cells without exposure to known mutagens
- These mutations result from errors in DNA replication or spontaneous changes in the chemical structure of a nucleotide base
- Spontaneous mutations provide a background mutation rate that varies among species and among genes
DNA Replication Errors
- DNA replication has high fidelity due to proofreading by DNA polymerases
- Genomic regions containing repeat sequences experience higher levels of error during replication
- This results in changes in the number of base pairs in repeating sequences
DNA Repeat Mutations
- Alterations in the number of DNA repeats occur via strand slippage
- DNA polymerase temporarily dissociates from the template, and a portion of the newly replicated DNA forms a temporary hairpin
- Resumption of replication leads to re-replication of some of the repeats and an overall increase in the number of repeats on the daughter strand
Spontaneous Nucleotide Base Changes
- DNA nucleotides can convert to alternative structures called tautomers with slight differences in bonding and placement of hydrogens
Spontaneous Nucleotide Base Changes
- Tautomeric shifts can lead to base-pair mismatches and incorporation of incorrect bases during replication
- This is the most common form of replication error
Mutations May Be Induced by Chemicals or Radiation
- Induced mutations are produced by interactions between DNA and physical, chemical, or biological agents that generate mutations
- Agents that cause DNA damage leading to mutations are called mutagens
- Mutagens interact with DNA in specific ways to cause particular types of sequence changes
- Chemical mutagens can be classified by how they modify DNA
Chemical Mutagens
- The high frequencies of mutant alleles suggest that natural selection maintains their prevalence
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Description
This quiz explores the classification of chemical mutagens and the various DNA repair systems, including mismatch repair, photoreactivation repair, base excision repair, and nucleotide excision repair. Test your knowledge on how these mechanisms work to correct DNA damage.
