MUTATIONS & DNA REPAIR

What is a point mutation?

A change to a single nucleotide pair in DNA.

What is a silent mutation?

A mutation that changes a codon but does not change the amino acid encoded.

What is a missense mutation?

A mutation that changes one amino acid to another.

What is a conservative missense mutation?

A substitution that results in an amino acid with similar chemical properties.

What is a nonconservative missense mutation?

A substitution that results in an amino acid with very different properties.

What is a nonsense mutation?

A mutation that converts a codon into a premature stop codon.

What is a frameshift mutation?

Addition or deletion of nucleotides not in multiples of three, altering the reading frame.

What type of mutation has the most drastic effect on protein function?

Frameshift mutations, because they change all downstream amino acids.

What is a neutral mutation?

A mutation that has no effect on organismal fitness.

What is a deleterious mutation?

A mutation that decreases fitness.

What is a beneficial mutation?

A mutation that increases fitness in a given environment.

What are indels?

Insertions or deletions of nucleotides.

What typically causes spontaneous mutations?

Errors during DNA replication or spontaneous chemical changes like depurination.

What is depurination?

Spontaneous loss of a purine base (A or G) from DNA.

What is deamination?

Conversion of cytosine to uracil by removal of an amino group.

What is a mutagen?

An environmental agent that increases mutation rate (e.g., UV, radiation, chemicals).

How does UV light cause mutations?

Forms thymine dimers that distort DNA and block replication.

What type of mutation do X-rays commonly cause?

Double-strand breaks or large chromosomal abnormalities.

What is a tautomeric shift?

A rare shift in base structure causing mispairing during replication.

What is mismatch repair (MMR)?

A repair pathway that fixes mismatched bases after replication using strand-specific signals.

How does mismatch repair identify the newly synthesized strand in bacteria?

The old strand is methylated; the new strand is not yet methylated.

What is nucleotide excision repair (NER)?

Removes bulky lesions (e.g., thymine dimers) by cutting out a segment of damaged DNA.

What disorder is caused by defects in NER?

Xeroderma pigmentosum, leading to extreme UV sensitivity.

What is base excision repair (BER)?

Replaces damaged bases (e.g., uracil from deamination) using DNA glycosylases.

What enzyme removes damaged bases in BER?

DNA glycosylase.

What type of damage does BER fix?

Small, non-bulky base modifications.

What is the function of AP endonuclease?

Cuts DNA backbone at abasic (AP) sites after glycosylase removes the base.

Why is double-strand break repair important?

DSBs can lead to chromosomal loss or rearrangements if not repaired.

What is non-homologous end joining (NHEJ)?

DSB repair where ends are directly ligated; error-prone.

What is homologous recombination repair (HRR)?

DSB repair using a sister chromatid as a template; high fidelity.

When can HRR occur?

During S or G2 phase when sister chromatids are present.

Why is NHEJ considered mutagenic?

It often removes or adds a few nucleotides at the break site.

What is a mutational hotspot?

A DNA region with a high mutation frequency.

What is a suppressor mutation?

A second mutation that restores function lost due to an earlier mutation.

What is a reversion mutation?

A mutation that restores the original sequence.

What is a forward mutation?

A mutation that changes the wild-type allele to a mutant allele.

What is a backward mutation?

Also called reversion; returns mutant allele to wild type.

How does oxidative damage cause mutations?

Reactive oxygen species modify bases, causing mispairing.

What enzyme repairs alkylation damage?

Alkyltransferase enzymes remove alkyl groups from bases.

What are translesion polymerases?

Error-prone polymerases that replicate across damaged DNA when normal polymerases stall.

Why are translesion polymerases important?

Prevent replication fork collapse but introduce mutations.

What is the consequence of failing to repair a replication error before the next round of replication?

The mutation becomes permanently fixed in the genome.

Why do mutations in regulatory regions matter?

They alter gene expression levels rather than protein sequence.

How can mutations in splice sites affect proteins?

They can cause exon skipping or intron retention, altering the reading frame.

Why are mutations in germ cells more evolutionarily important?

They can be passed to offspring.

Why are mutations in somatic cells not inherited?

They occur after fertilization and affect only the individual.

What is a dominant negative mutation?

A mutant protein interferes with the function of the wild-type protein.

What type of mutation creates a new enhancer or promoter site?

Gain-of-function regulatory mutation.

What is a null mutation?

A mutation that completely abolishes gene function.