Biology Chapter 10: DNA Mutability and Repair

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Questions and Answers

What mechanisms contribute to the low mutation rate of DNA, and why is this rate critical for genetic material?

The low mutation rate is maintained through error-checking during DNA replication and repair mechanisms. This rate is critical for ensuring the accurate transmission of genetic information across generations.

Describe the difference between transitions and transversions in the context of DNA mutations.

Transitions involve the substitution of a pyrimidine for a pyrimidine or a purine for a purine, while transversions involve the substitution of a pyrimidine for a purine or vice versa.

What role do transposons play in DNA mutations, and how can they affect genetic stability?

Transposons, or 'jumping genes,' can insert themselves into various locations within the genome, causing mutations or disrupting gene function. Their activity can lead to genetic instability and variability within populations.

How do cells differentiate between the parental and daughter strands during DNA repair?

Cells distinguish the parental strand from the daughter strand using specific markers such as DNA methylation patterns that are characteristic of the original template DNA. Signup and view all the answers

Why is a balance between mutation and repair considered vital for biodiversity and evolution?

A balance between mutation and repair fosters genetic diversity essential for natural selection and adaptation, driving the formation of new species while maintaining genomic integrity. Signup and view all the answers

What are the consequences of extensive insertions or deletions in chromosome structure?

They cause drastic changes in DNA. Signup and view all the answers

What is considered a 'hot spot' for mutations in DNA?

'Hot spots' are areas where mutations occur at a high frequency, such as DNA microsatellites. Signup and view all the answers

Explain the role of the DNA replication proofreading function.

It helps to correct misincorporated nucleotides during DNA synthesis. Signup and view all the answers

How does the mismatch repair system enhance DNA synthesis accuracy?

It rapidly scans for mismatches and corrects them accurately on the newly synthesized strand. Signup and view all the answers

What is the function of MutS in E. coli's mismatch repair system?

MutS detects mismatches in the DNA. Signup and view all the answers

Describe the role of Dam methylase in the mismatch repair process.

Dam methylase adds a methyl group to adenine residues in the parental strands. Signup and view all the answers

What happens at hemimethylated sites during mismatch repair?

MutH binds to hemimethylated sites and nicks the unmethylated strand. Signup and view all the answers

Identify the two main challenges faced by the mismatch repair system.

Rapid scanning for mismatches and accurate correction of the newly synthesized strand. Signup and view all the answers

What natural base is generated from the deamination of cytosine in DNA that contains uracil?

Thymine is generated from the deamination of cytosine. Signup and view all the answers

What type of mutation is primarily caused by alkylation of DNA bases?

Alkylation can generate methylguanine, which mispairs with thymine. Signup and view all the answers

How does oxidative stress lead to the formation of oxoguanine?

Reactive oxygen species oxidize guanine, resulting in oxoguanine. Signup and view all the answers

What type of DNA damage is caused by ultraviolet radiation?

Ultraviolet radiation causes the formation of thymine dimers. Signup and view all the answers

What type of DNA damage do γ-radiation and X-rays primarily cause?

They primarily cause double-strand breaks in the DNA. Signup and view all the answers

What is the role of base analogs like 5-bromouracil in DNA replication?

Base analogs are incorporated into DNA and can lead to inaccurate base-pairing. Signup and view all the answers

Describe the mechanism by which intercalating agents induce mutations.

Intercalating agents slip between DNA bases, causing insertions or deletions. Signup and view all the answers

What is the significance of bleomycin as an anticancer drug in relation to DNA?

Bleomycin causes breaks in DNA, targeting rapidly dividing cells. Signup and view all the answers

What are two consequences of DNA damage related to thymine dimers?

Thymine dimers can block DNA replication and transcription. Signup and view all the answers

How does deamination of cytosine lead to a transition mutation?

Deamination of cytosine results in a conversion from C:G to T:A, creating a transition mutation. Signup and view all the answers

Describe the role of Photolyase in DNA repair.

Photolyase uses energy from light to break the covalent bonds linking pyrimidines in thymine dimers. Signup and view all the answers

What is the primary function of glycosylases in base excision repair?

Glycosylases hydrolyze the glycosidic bond of damaged bases, allowing for their removal. Signup and view all the answers

What distinguishes nucleotide excision repair from base excision repair?

Nucleotide excision repair cleaves DNA on either side of a lesion, while base excision repair targets individual damaged bases. Signup and view all the answers

Explain the transition mechanism of Translesion Polymerase during DNA synthesis.

Translesion Polymerase synthesizes DNA across the site of damage, allowing replication to continue despite DNA lesions. Signup and view all the answers

What happens when a damaged base is not removed during base excision repair?

If not removed, the oxoG:A pair may form, potentially causing a mispairing during replication. Signup and view all the answers

In the context of DNA damage repair, what function does the methyltransferase serve?

Methyltransferase removes the methyl group from methylguanine, transferring it to its own cysteine residue. Signup and view all the answers

What are the functions of Exonuclease VII and RecJ in mismatch repair?

They degrade DNA in the 5' to 3' direction, specifically removing mismatched DNA cleaved on the 5' side of the mismatch. Signup and view all the answers

How does Exonuclease I differ from Exonuclease VII in terms of its function?

Exonuclease I degrades DNA in the 3' to 5' direction and is used when the nick is on the 3' side of the mismatch. Signup and view all the answers

What role do MSH proteins play in eukaryotic cells during mismatch repair?

MSH proteins recruit mismatch repair proteins to both the lagging and leading strands to facilitate the repair process. Signup and view all the answers

What is the consequence of MutS and MutL mutations in higher organisms?

Mutations in MutS and MutL can lead to an increased risk of colon cancer. Signup and view all the answers

What factors can lead to DNA damage according to the provided information?

DNA damage can occur due to spontaneous hydrolysis, environmental factors like radiation, and chemical mutagens. Signup and view all the answers

Why is cytosine deamination considered significant in DNA damage?

Cytosine deamination generates uracil, an unnatural base in DNA, which can disrupt pairing and lead to mutations. Signup and view all the answers

Explain the significance of having thymine instead of uracil in DNA.

Thymine helps in distinguishing between natural and damaged bases, reducing the occurrence of mutations. Signup and view all the answers

What is the Ames Test and what does it measure?

The Ames Test is used to identify potential mutagens by measuring their effect on mutation frequency in bacteria. Signup and view all the answers

What roles do UvrA and UvrB play in nucleotide excision repair in E. coli?

UvrA and UvrB scan the DNA for lesions. Signup and view all the answers

Describe the function of UvrC in the nucleotide excision repair process.

UvrC creates two incisions, one 4-5 nucleotides 3’ and another 8 nucleotides 5’ to the lesion. Signup and view all the answers

What is the role of RNA polymerase in transcription-coupled repair?

RNA polymerase scans for DNA damage and recruits nucleotide excision repair proteins when it encounters lesions. Signup and view all the answers

Explain how XPC contributes to nucleotide excision repair in eukaryotes.

XPC detects distortions in the DNA helix. Signup and view all the answers

What is the significance of TFIIH during transcription-coupled DNA repair?

TFIIH unwinds the DNA template and includes helicase activity for lesion melting. Signup and view all the answers

What is non-homologous end joining (NHEJ) and why is it considered mutagenic?

NHEJ processes broken ends and joins them, but sequence information is lost, making it mutagenic. Signup and view all the answers

Identify two proteins involved in eukaryotic nucleotide excision repair and their functions.

XPA forms a bubble by helicase activity, and ERCC1-XPF cuts DNA 5’ to the lesion. Signup and view all the answers

What are the consequences of double-strand breaks (DSBs) in DNA, and how are they repaired?

DSBs can block replication and cause cell death, repaired by non-homologous end joining or homologous recombination. Signup and view all the answers

Study Notes

Chapter 10: The Mutability and Repair of DNA

DNA mutability and repair are crucial for the perpetuation of genetic material across generations
Mutations at protein-coding sequences or mRNA regulatory regions alter cellular phenotypes
Genetic variations are important factors in evolution and biodiversity

Replication Errors and Their Repair

Replication errors escape proofreading sometimes
Spontaneous mutation rates are typically low, ranging from 10^-6 to 10^-11 per round of DNA replication
"Hot spots" exist where mutations occur at higher frequencies, exemplified by microsatellites (repeating di-, tri-, or tetranucleotide sequences)
These CA repeats are often found in eukaryotes, and are hard to copy with high fidelity
Mutations can lead to changes in the number of copies in the genome. They can also be highly polymorphic and used as markers for inherited mutations, such as in the case of microsatellites.
DNA replication machinery has proofreading capability (3'→5' exonuclease activity), but some errors escape detection
Mismatch repair systems correct errors that escape proofreading, by quickly scanning the genome for mismatches and accurately correcting newly synthesized strands.
E. coli has a MutS dimer that recognizes mismatches, triggering a conformational change and recruitment of the repair complex (MutL, MutH)
MutH nicks the unmethylated strand, guiding excision of the incorrect base

DNA Damage

DNA can be damaged spontaneously through hydrolysis and deamination
Environmental factors, such as radiation, and chemical mutagens can further increase the frequency of damage
Deamination of cytosine creates uracil, a non-standard DNA base
Deamination of adenine yields hypoxanthine, and deamination of guanine forms xanthine. Hydrolytic reactions result in abnormal alterations
DNA can be damaged via alkylation (methyl/ethyl groups), oxidation (reaction oxygen species), and radiation (e.g., UV, γ radiation, and X-rays)
UV radiation causes thymine dimers, impeding DNA replication, and other forms of radiation cause double-strand breaks in DNA

Repair and Tolerance of DNA Damage

Cells must repair DNA damage to prevent blocking replication or inducing mutations
Excision repair removes damaged nucleotides
Recombination repair corrects double-strand breaks.
Translesion DNA synthesis allows replication to continue through damaged areas, but this process is error-prone and can introduce mutations.
DNA polymerase III's role in replication is challenged by DNA damage
Photoreactivation enzymes directly reverse some damage such as thymine dimers.
Methyltransferases remove alkyl groups from bases, and these processes protect against further damage
Base excision repair removes damaged bases via a glycosylase removing the base, then a series of steps remove and replace the damaged segment on the repaired DNA strand.
Nucleotide excision repair removes bulky lesions that distort the DNA helix (thymine dimers)
Eukaryotic nucleotide excision repair is similar to E. coli repair but involves more proteins. For example proteins involved in the eukaryotic repair process include XPC, XPA, XPD, RPA, ERCC1-XPF and XPG.
Transcription-coupled repair utilizes RNA polymerase to identify and fix DNA damage
Non-homologous end joining (NHEJ) is used repair double-strand breaks in DNA, which can cause serious consequences, including cell death, if left unfixed.
Translesion synthesis allows DNA polymerase to bypass DNA damage, but is error-prone, leading to mutations

Summary of DNA Polymerases

Different families of DNA polymerases exist for various scenarios
Translesion polymerases are specific for bypassing damage
Translesion polymerases are heavily regulated. In E. coli, their expression is induced by DNA damage, such as in the SOS response, that degrades the repressors of these proteins; for example, the repressor LexA regulates DinB, UmuC, and UmuD.

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Description

This quiz explores the intricacies of DNA mutability and the mechanisms of DNA repair. Understand how genetic variations influence evolution and the significance of replication errors in genetic fidelity. Test your knowledge on mutations, hotspots, and their implications in genetics.