mutations and DNA damage

What is a mutation?

A heritable change in genetic material, involving DNA sequence, gene copy number, or chromosome structure.

What are the main categories of mutations?

Gene mutations, gene duplications/amplifications, chromosome aberrations, and changes in chromosome number.

What is a point mutation?

A change in a single base pair in DNA.

What are transitions in point mutations?

Purine → purine or pyrimidine → pyrimidine substitutions.

What are transversions in point mutations?

Purine → pyrimidine or pyrimidine → purine substitutions.

What is a frameshift mutation?

Insertions or deletions that shift the reading frame of a gene.

What are the two major sources of mutations?

Spontaneous mutagenesis and induced mutagenesis.

What causes spontaneous mutagenesis?

Replication errors, spontaneous chemical changes, and endogenous DNA damage.

What are replication mismatches?

Incorrect base pairing during replication that escapes proofreading and repair.

What is replication slippage?

Looping out of DNA strands during replication, causing insertions or deletions.

Which disease is linked to trinucleotide repeat expansion via slippage?

Huntington’s disease.

What is cytosine deamination?

Conversion of cytosine to uracil, causing CG → TA transition mutations.

Why is cytosine deamination directly mutagenic?

Uracil pairs with adenine, leading to base substitution after replication.

What increases cytosine deamination rates?

Nitrous acid.

What is aberrant base methylation?

Incorrect methylation of DNA bases by reactive methyl donors like SAM.

What is O6-methylguanine (O6-meG)?

A miscoding lesion that causes GC → AT transition mutations.

Why is O6-meG considered mis-informational damage?

It can base pair incorrectly without blocking DNA replication.

What are N7-methylguanine and N3-methyladenine?

Non-informational DNA lesions that block DNA polymerase.

What is oxidative DNA damage?

DNA damage caused by reactive oxygen species (ROS).

What is 8-oxoguanine?

An oxidized base that can mispair with adenine, causing GC → TA transversions.

Why is 8-oxoguanine directly mutagenic?

It does not block replication and causes mispairing.

What is the difference between mis-informational and non-informational DNA damage?

Mis-informational damage causes direct base substitutions; non-informational damage blocks replication.

What are single-strand breaks (SSBs)?

Breaks in one DNA strand that are common and easy to repair.

What are double-strand breaks (DSBs)?

Breaks in both DNA strands that are rare but difficult to repair.

Why are interstrand crosslinks dangerous?

They damage both DNA strands and block replication and transcription.

What causes induced mutagenesis?

Environmental mutagens like radiation and chemicals.

What types of radiation cause DNA damage?

UV light, X-rays, and gamma rays.

What DNA lesions are caused by UV radiation?

Pyrimidine dimers and 6–4 photoproducts.

Why are pyrimidine dimers dangerous?

They distort DNA and block replication and transcription.

What is translesion synthesis (TLS)?

Error-prone DNA replication across damaged templates.

Why does TLS increase mutation risk?

The polymerase inserts bases randomly at damaged sites.

What is ionising radiation?

High-energy radiation that causes base damage and DNA strand breaks.

Why is ionising radiation a clastogen?

It causes chromosome breaks and large deletions.

What is nitrous acid classified as?

A chemical mutagen that promotes cytosine deamination.

What do alkylating agents do?

Add alkyl groups to DNA bases, causing miscoding or blocking lesions.

Which alkylation lesion causes GC → AT transitions?

O6-methylguanine.

What are arylating agents?

Chemicals that form bulky DNA adducts after metabolic activation.

Why do arylating agents require metabolic activation?

They are converted into DNA-reactive forms by cytochrome P450 enzymes.

What is an example of a dietary arylating agent?

Aflatoxin B1.

What do intercalating agents cause?

Frameshift mutations.

How do intercalating agents cause mutations?

By inserting between DNA bases and altering replication spacing.

What do interstrand crosslinking agents do?

Covalently link both DNA strands together.

Why is DNA damage not the same as mutation?

DNA damage can be repaired; mutations are permanent

When does DNA damage become a mutation?

When it is replicated before repair.