Biology Chapter 10: DNA Mutability and Repair

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Questions and Answers

What is a consequence of DNA damage that can block replication and transcription?

Base mispairing

C:G to A:T transition mutation

Thymine dimers (correct)

Deamination of adenine

Which DNA repair mechanism directly removes damaged nucleotides?

Nucleotide excision repair

Base excision repair (correct)

Translesion polymerase synthesis

Recombinational repair

What is the role of photolyase in DNA repair?

It synthesizes DNA across damage sites.

It captures energy from light to reverse damage. (correct)

It cleaves damaged DNA on either side.

It transfers methyl groups to damaged bases.

In nucleotide excision repair, what triggers the recognition of damaged DNA?

Distortions in the double helix structure Signup and view all the answers

Which process synthesizes DNA across damaged sites within the DNA?

Translesion polymerase synthesis Signup and view all the answers

What is a fail-safe system in DNA repair concerning oxidized guanine?

Base excision repair Signup and view all the answers

How does DNA methyltransferase function in DNA damage repair?

It transfers methyl groups to bases. Signup and view all the answers

Which type of DNA damage is specifically repaired through excision mechanisms?

Thymine dimers Signup and view all the answers

Which protein is responsible for detecting distortions in the DNA helix during nucleotide excision repair in eukaryotes?

XPC Signup and view all the answers

What is the function of UvrD in the DNA repair process?

Removes the strand containing the lesion Signup and view all the answers

What is a characteristic of the non-homologous end joining (NHEJ) repair mechanism?

Protects and processes broken ends before joining them Signup and view all the answers

Which proteins form a bubble around the lesion during nucleotide excision repair?

XPA and XPD Signup and view all the answers

In transcription-coupled repair, what happens when RNA polymerase encounters damaged DNA?

It recruits repair proteins and stalls transcription Signup and view all the answers

What is the primary function of the UvrC protein in E. coli's excision repair mechanism?

To create incisions around the lesion Signup and view all the answers

How do eukaryotic cells typically repair double-strand breaks (DSB) in DNA?

By joining the broken ends directly with NHEJ Signup and view all the answers

Which repair mechanism is most cytotoxic to cells due to its blocking of DNA replication?

Double-strand break repair Signup and view all the answers

What are the proteins involved in non-homologous end joining (NHEJ)?

Ku70, Ku80, DNA-PKcs, Artemis, XRCC4, Cernunnos-XLF, DNA ligase IV Signup and view all the answers

What role does Artemis play in the NHEJ mechanism?

It acts as a 5’->3’ exonuclease and endonuclease. Signup and view all the answers

What occurs during translesion DNA synthesis?

DNA polymerases synthesize DNA across the site of damage, introducing mutations. Signup and view all the answers

How does E. coli regulate the expression of translesion DNA polymerases under normal conditions?

They are repressed by LexA until DNA damage occurs. Signup and view all the answers

Which of the following statements about translesion synthesis is accurate?

It is performed by a specialized class of DNA polymerase. Signup and view all the answers

What is the primary function of DNA ligase IV in the NHEJ pathway?

It performs the ligation of processed DNA ends. Signup and view all the answers

What defines the nature of translesion polymerases in bypassing DNA damage?

They can incorporate nucleotides without base pairing specificity. Signup and view all the answers

Which of the following statements best describes the SOS response in E. coli?

It facilitates the expression of translesion DNA polymerases after DNA damage. 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 and driving evolution.
A low mutation rate is essential for the maintenance of genetic information across generations.
Mutations occurring in protein-coding sequences or DNA regions controlling mRNA expression can alter cell phenotypes.
Changes in DNA sequences/genetic variations are critical for evolution and the emergence of new species, especially humans.
Biodiversity depends on a balance between mutation rates and repair mechanisms.

Important Sources of DNA Mutations

Inaccuracies during DNA replication.
Chemical damage to DNA.
Insertion of DNA elements (transposons).

Errors in DNA Replication and Damage to DNA

Permanent changes to DNA, known as mutations, can result from replication errors or damage.
Mutations can prevent or disrupt DNA replication or transcription.
This chapter explores how cells detect, repair, and tolerate DNA alterations.

Replication Errors and Their Repair

This section describes the nature of mutations, categorized as:
- Transitions: pyrimidine to pyrimidine or purine to purine changes (e.g., T to C, A to G).
- Transversions: pyrimidine to purine or purine to pyrimidine changes (e.g., T to A, C to G).
- Insertions or deletions of single nucleotides.
Extensive insertions, deletions, or chromosome structural rearrangements cause significant changes in DNA.
Spontaneous mutations occur at a rate of 10⁻⁶ to 10⁻¹¹ per round of DNA replication. Specific regions, known as "hotspots," have elevated mutation frequencies.
Exemplary hotspots include microsatellites, repetitive DNA sequences like CA repeats, which are prone to errors in copying and show high polymorphism, aiding in identifying inherited mutations.

Mismatch Repair

Mismatch repair systems increase the accuracy of DNA synthesis.
Two key challenges of mismatch repair are scanning the genome for mistakes and accurately correcting mismatches, primarily in newly synthesized DNA strands.
MutS dimer detects mismatched DNA (distorted structures) triggering a conformational change and recruiting MutL (another repair component).
MutL activates MutH, an enzyme creating an incision or nick near the mismatch, enabling the removal of the wrong nucleotide.

DNA Damage

DNA damage can occur spontaneously through hydrolysis and deamination.
Environmental factors like radiation and chemical mutagens can also cause DNA damage.
Mutations can derive either from replication errors, or from damage to DNA itself.

Deamination of Cytosine

Deamination is a frequent type of hydrolytic damage, converting cytosine to uracil. This event occurs under normal conditions and generates an unnatural base in DNA, potentially leading to mutations.
Deamination of other bases, such as adenine and guanine, also alters base pairing properties.

Identifying Potential Mutagens (Ames Test)

The Ames test is a method for identifying potential mutagens.

Repair and Tolerance of DNA Damage

DNA damage must be repaired to avoid hindering replication and causing mutations or cell death.
Two significant consequences of DNA damage include thymine dimers and the deamination of cytosine.
Three major repair mechanisms are excision repair, recombinational repair, and translesion synthesis.

DNA Damage Repair and Tolerance Systems

Several specific enzymes and proteins play roles in DNA repair.
This section lists different types of DNA damage and the corresponding repair mechanisms, indicating the enzymes or protein complexes specific for each.

Direct Reversal of DNA Damage

Photoreactivation repairs thymine dimers by using light energy.
Removal of methyl groups from methylguanine by methyltransferases.

Base Excision Repair

Glycosylases initiate base excision repair by removing damaged bases. This process results in an abasic sugar, which is then removed, and the gap filled by DNA polymerase and DNA ligase.
Specific glycosylases target unique kinds of damage (e.g., uracil, oxo guanine).

Nucleotide Excision Repair

Specialized proteins scan DNA for distortions in the double helix shape caused by damage (e.g., thymine dimers or bulky chemical adducts).
Incisions are made on either side of the damage, and the damaged segment is removed, leaving a gap that is repaired by DNA polymerase and DNA ligase.

Transcription-Coupled Repair

If DNA damage occurs within the gene region, RNA polymerase can halt transcription.
RNA polymerase can recruit nucleotide excision repair proteins with the help of TFIIH protein, which unwinds the DNA template.

Recombination Repair

Recombination repair uses undamaged DNA as a template to replace damaged DNA segments.

Non-Homologous End Joining (NHEJ)

This mechanism is a critical repair pathway for double-strand breaks.
NHEJ joins the broken ends of DNA without precise restoration of the original sequence.

Translesion Synthesis

This process allows DNA replication to proceed across damaged sites but is highly error-prone.
Specialized DNA polymerases (e.g., Pol IV or V in E. coli) are responsible for translesion synthesis. This process generates mutations that need repair.

Mechanisms for Regulation of Translesion Synthesis

Translesion DNA polymerases are not expressed under normal conditions. They are induced by specific kinds of DNA damage through transcriptional mechanisms like the "SOS response."
Tight regulation is imposed to limit the highly mutagenic nature of translesion synthesis.

How Translesion Polymerases Access DNA Damage Sites

In eukaryotes, chemical modification of the sliding clamp facilitates the binding and incorporation of translesion polymerases at damaged sites.

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Description

This quiz covers Chapter 10, focusing on the mutability and repair of DNA. It explores the importance of mutation rates, the sources of DNA mutations, and the mechanisms cells use to repair these changes. Understanding these concepts is essential for grasping the evolution of species and genetic information maintenance.