Molecular Biology: Base Excision Repair

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Questions and Answers

What defines a mutation in genetics?

A stable and heritable change in a DNA sequence (correct)

A temporary change in RNA sequence

An alteration that does not affect phenotype

A random error in DNA replication

What is a hypomorph?

A mutant with some residual activity, but less than wildtype (correct)

A mutant that fully mimics the wildtype phenotype

A mutant that produces no gene product

A mutant with excess normal protein product

Which of the following statements describes nullomorphs?

They have increased gene expression

They are equivalent to a full deletion of the gene (correct)

They produce a partially functional gene product

They are always dominant mutations

How do antimorphic mutations affect the wildtype protein?

They produce a protein that antagonizes the wildtype protein Signup and view all the answers

In Muller's classification, which type of mutant is expected to have a dominant effect?

Antimorphs Signup and view all the answers

Which statement about hypermorphs is true?

They produce hyperactive protein products Signup and view all the answers

What phenotype is observed in individuals with M2/+ genotype?

Mutant phenotype Signup and view all the answers

Which of the following accurately describes a semidominant mutation?

More severe phenotype in homozygotes than in heterozygotes Signup and view all the answers

What is the term for the frequency with which a wild-type allele changes into a mutant allele?

Mutation rate Signup and view all the answers

Which of the following is a loss-of-function mutation effect?

Complete loss of protein function Signup and view all the answers

Which type of mutation specifically compensates for the effects of another mutation?

Suppressor mutation Signup and view all the answers

What is the mutation rate for achondroplasia, expressed as mutations per gamete?

4 per 100,000 Signup and view all the answers

What mechanism involves mispairing due to tautomeric shifts?

Spontaneous replication errors Signup and view all the answers

Why might eukaryotic mutation rates appear higher compared to prokaryotic rates?

They include multiple cell divisions before gamete formation Signup and view all the answers

Which of the following adequately describes a neutral mutation?

It has no significant impact on organism function Signup and view all the answers

Which of the following represents a type of spontaneous chemical change that leads to mutations?

Depurination Signup and view all the answers

What was the primary purpose of the Luria and Delbrück fluctuation test?

To prove that mutations are random occurrences Signup and view all the answers

Which organism is commonly used in the Ames test for detecting mutagenicity?

Salmonella typhimurium Signup and view all the answers

What type of mutation do all four strains used in the Ames test detect?

Base-pair substitutions and frameshift mutations Signup and view all the answers

What is suggested by a lower rate of mutation in a genomic context?

Higher efficiency of DNA repair systems Signup and view all the answers

What role do enzymes like alkyltransferases play in DNA repair?

They directly reverse specific types of DNA damage Signup and view all the answers

Which repair mechanism is directly involved in correcting double-strand breaks in DNA?

Homology-dependent repair systems Signup and view all the answers

What is the main function of DNA glycosylases in base excision repair?

To recognize and remove damaged bases Signup and view all the answers

Which factor does NOT contribute to DNA damage?

Reverse transcription Signup and view all the answers

What proportion of all DNA repairs is encompassed by mismatch repair?

99% Signup and view all the answers

Which gene is also known as uvrD in the context of mismatch repair?

mutU Signup and view all the answers

What mechanism utilizes the sister chromatid to repair double-strand breaks?

Homologous recombination Signup and view all the answers

Which repair mechanism is triggered in response to spontaneous double-strand breaks?

Nonhomologous end joining Signup and view all the answers

Which syndrome is characterized by an inability to repair thymine dimerization caused by UV light?

Xeroderma pigmentosum Signup and view all the answers

What is the role of RAD51 in homologous recombination?

To search for complementary sequences Signup and view all the answers

Which enzyme is responsible for removing uracil produced by the deamination of cytosine?

Uracil glycosylase Signup and view all the answers

Which of the following describes the genetic inheritance pattern of Xeroderma pigmentosum?

Autosomal recessive trait Signup and view all the answers

In the context of double-strand break repair, which mechanism is NOT utilized?

Nucleotide excision repair Signup and view all the answers

What is the error rate of DNA polymerase β when inserting nucleotides?

1 mistake per 4000 nucleotides Signup and view all the answers

Which component is involved in contact with transcription-coupled repair in eukaryotes?

Transcription factor TFIIH Signup and view all the answers

What type of DNA damage does nucleotide excision repair primarily address?

Distortions in the DNA backbone Signup and view all the answers

How many proteins are involved in the nucleotide excision repair process in humans?

25 proteins Signup and view all the answers

What does the mismatch-repair system do in DNA replication?

Detect mismatched base pairs Signup and view all the answers

What consequence does DNA polymerase β have on the human genome?

It introduces approximately 10 mutations per day. Signup and view all the answers

Which process is primarily responsible for repairing replication errors that escape the proofreading function?

Postreplication repair Signup and view all the answers

Study Notes

Mutation Basics

A mutation is a stable and heritable change in a DNA sequence.
Mutations create phenotypes distinct from the wildtype allele, which can arise from base substitutions, duplications, deletions, or chromosomal aberrations like inversions and translocations.

Classification of Mutations

Dominant mutations (M2) can express a mutant phenotype in heterozygotes, while recessive mutations (m1) typically yield a wildtype appearance in heterozygotes.
Semidominant mutations showcase varying severity in homozygotes compared to heterozygotes.

Muller's Classification of Mutants

Developed by H.J. Muller in 1932, this classification includes:
- Nullomorphs: Complete loss of gene function.
- Hypomorphs: Reduced gene function, insufficient for wildtype phenotype.
- Hypermorphs: Enhanced or excess gene activity.
- Antimorphs: Mutations that inhibit wildtype protein function.
- Neomorphs: Mutations that create new functions.

Types of Mutants

Nullomorphs: No functional gene product remains; can have various defects in gene expression.
Hypomorphs: Produce residual activity but insufficient to manifest a normal phenotype, often recessive.
Hypermorphs: Generate overactive protein products or excess normal proteins; useful for examining genetic processes.
Antimorphs: Produce products that negatively affect wildtype function; typically dominant.

Mutations Overview

They can be classified into loss-of-function and gain-of-function mutations.
Essential terms include wild-type phenotype, forward and reverse mutations, and neutral mutations.

Suppressor Mutations

Intragenic suppressor mutations occur within the same gene, compensating for previous mutations.
Intergenic suppressor mutations occur in different genes and can also counteract mutations.

Mutation Rate

The mutation rate indicates how frequently wild-type alleles convert to mutant alleles, expressed per cell division or gamete.
Factors influencing mutation rates include the occurrence of primary DNA changes and probabilities related to mutation detection.
Mutation rates for viral and bacterial organisms are approximately 1 to 100 mutations per 10 billion cells, while eukaryotic genes show rates of 1 to 10 mutations per million gametes.

Causes of Mutations

Spontaneous replication errors:
- Tautomeric shifts, wobble formation, strand slippage, unequal crossing over.
Spontaneous chemical changes:
- Depurination and deamination.

Detection of Mutations

Luria and Delbrück fluctuation test helps establish spontaneous mutation rates.
Ames test (1974) uses Salmonella typhimurium to detect mutagenicity, focusing on reversions of specific mutations.

DNA Damage and Repair

DNA damage can result from radiation, chemical mutagens, and spontaneous decay.
More than 99% of DNA lesions are repaired, and various pathways exist for DNA repair:
- Direct reversal mechanisms (alkyltransferases).
- Base excision repair (specific glycosylases address modified bases).
- Nucleotide excision repair (removes bulky lesions).
- Mismatch repair systems based on recognition and correction of errors in DNA replication.

Nonhomologous End-Joining and Homologous Recombination

Double-strand breaks can be repaired by nonhomologous end-joining or homologous recombination.
Homologous recombination uses the sister chromatid as a template to repair broken strands.

Faulty DNA Repair Examples

Xeroderma pigmentosum: Autosomal recessive disorder linked to failure in repairing UV-induced thymine dimers, leading to high skin cancer risk.
Li-Fraumeni syndrome: Associated with mutations in p53, increasing propensity for various cancers due to impaired cell cycle regulation and DNA repair mechanisms.

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Description

Explore the intricate processes of base excision repair in this quiz. Dive into the roles of uracil glycosylase and AP endonuclease, understanding how these enzymes interact with modified bases in both prokaryotic and eukaryotic systems. Test your knowledge on the mechanisms of DNA repair at a molecular level.