Gene Mutations and DNA Repair – Lecture Review

These flashcards review definitions, mechanisms, examples, and key proteins related to DNA mutations, their formation, repair pathways, and transposable elements.

What is a mutation?

A change in the base-pair sequence of DNA that can occur in gene coding regions or regulatory regions.

Why are mutations considered the raw material of natural selection?

They create genetic variability, producing different alleles that may confer selective advantages or adaptations.

What single-base change converts one base pair into a different base pair?

A point mutation (base substitution).

Which mutation changes a codon so that it codes for a different amino acid?

Missense mutation.

Which mutation converts a codon into a stop codon and prematurely terminates translation?

Nonsense mutation.

Which mutation changes a codon but still encodes the same amino acid?

Silent mutation.

What do we call a mutation occurring in non-coding DNA that has no phenotypic effect?

Neutral mutation.

What is the difference between a transition and a transversion?

Transition: purine↔purine or pyrimidine↔pyrimidine swap; Transversion: purine↔pyrimidine swap.

What type of mutation results from nucleotide insertions or deletions that alter the reading frame?

Frameshift mutation.

Which mutation reduces or abolishes gene product function?

Loss-of-function mutation.

Which mutation gives the gene product a new or enhanced activity and is usually dominant?

Gain-of-function mutation.

What is a suppressor (compensatory) mutation?

A second mutation that alleviates or masks the effect of an earlier mutation.

What is a null mutation?

A mutation that causes complete loss of gene function.

How does a dominant-negative mutation act?

An inactive gene product from one allele interferes with the normal product from the other allele.

Where do somatic mutations occur and are they heritable?

In non-germline cells; they are not heritable.

Where do germ-line mutations occur and what is their inheritance pattern?

In gametes; they are transmitted to offspring.

Why are X-linked recessive mutations more often expressed in males?

Males are hemizygous (one X chromosome) so recessive alleles are not masked by a second X.

How are spontaneous mutations generated?

By normal cellular processes such as DNA polymerase errors, tautomeric shifts, base loss, or oxidative damage.

What causes induced mutations?

Exposure to external mutagens like chemicals or radiation.

What is the approximate uncorrected DNA polymerase error rate in humans?

About 1 in 1,000,000 nucleotides; repair lowers it to ~1 in 100,000.

What replication error involves looping of template or nascent strands and leads to insertions or deletions?

Polymerase slippage.

Name two human disorders associated with repeat-sequence slippage.

Huntington disease and Fragile X syndrome.

How do tautomeric shifts create mutations?

Rare base tautomers mispair during replication, leading to transition mutations after another round of replication.

What is depurination?

Spontaneous loss of a purine base from DNA, leaving an abasic site.

What is deamination?

Removal of an amino group from cytosine or adenine, converting them to uracil or hypoxanthine, respectively.

List three reactive oxygen species that can damage DNA.

Superoxide anion (O₂⁻), hydroxyl radical (•OH), hydrogen peroxide (H₂O₂).

How do base analogs act as mutagens?

They mimic normal bases but undergo more frequent tautomeric shifts, causing mispairing.

What is the mutagenic effect of alkylating agents?

They add CH₃ or other alkyl groups to bases, altering pairing and causing transitions.

How do intercalating agents induce mutations?

They wedge between stacked bases, distorting DNA and causing insertions or deletions during replication.

What are DNA adduct-forming agents?

Chemicals that covalently bind DNA, altering its conformation and hindering replication/repair.

How does UV radiation primarily damage DNA?

By forming pyrimidine dimers that block replication and transcription.

What makes ionizing radiation highly mutagenic?

It penetrates tissues and generates free radicals that break DNA strands.

Which enzyme performs 3’→5’ exonucleolytic proofreading during DNA synthesis?

DNA polymerase (I or III in bacteria).

What does the mismatch repair system use to identify the correct strand in bacteria?

Methylation patterns distinguishing parental (methylated) from newly synthesized (unmethylated) DNA.

Which protein mediates homologous recombination during post-replication repair of thymine dimers in E. coli?

RecA protein.

When is the SOS repair system induced and what is its consequence?

After extensive DNA damage; it allows replication to proceed but is error-prone, raising mutation rates.

Describe the steps of base-excision repair (BER).

DNA glycosylase removes the wrong base, an endonuclease cuts the backbone, DNA polymerase fills the gap, ligase seals it.

What distinguishes nucleotide-excision repair (NER) from BER?

NER removes a short oligonucleotide (≈13 bases in E. coli) containing bulky lesions or distortions, not just a single base.

Which repair pathway fixes double-strand breaks using an undamaged sister chromatid template?

Homologous recombination (HR) repair.

Which protein complex binds DNA ends during non-homologous end joining (NHEJ)?

Ku proteins.

Why is NHEJ considered error-prone?

It ligates DNA ends directly without a template, often causing small insertions or deletions.

Who discovered transposable elements and what are they commonly called?

Barbara McClintock; "jumping genes" or transposons.

What sequences flank many DNA transposons and are recognized by transposase?

Inverted terminal repeats (ITRs) flanked by direct repeats (DRs).

How do retrotransposons move within the genome?

Via an RNA intermediate using a copy-and-paste mechanism involving reverse transcriptase and integrase.

What is the evolutionary significance of transposable elements?

They generate genetic diversity, create new genes, and alter regulatory regions, influencing evolution.