Mutations, Mutagenesis and DNA Repair – Core Vocabulary

A set of vocabulary flashcards covering key terms related to mutations, mutagenesis mechanisms, DNA repair pathways, and associated human diseases discussed in the lecture.

Mutation

Any change in the nucleotide sequence of DNA.

Somatic mutation

DNA change arising in non-germline body cells; not inherited by offspring.

Germline mutation

DNA change that occurs in sperm or egg cells and is transmitted to every cell of the offspring.

Synonymous (silent) mutation

Base substitution in a coding exon that does not alter the encoded amino acid due to redundancy of the genetic code.

Non-synonymous mutation

Base substitution in a coding region that changes the encoded amino acid.

Missense mutation

Non-synonymous point mutation that substitutes one amino acid for another in a protein.

Nonsense mutation

Point mutation that converts a codon for an amino acid into a premature stop codon, truncating the protein.

Same-sense mutation

Point mutation that changes a codon to another codon for the same amino acid (synonymous).

Splice-site mutation

DNA change at exon–intron boundaries that disrupts normal RNA splicing, potentially adding introns or skipping exons.

Promoter mutation

Alteration in a gene’s promoter that affects transcription levels and therefore amount of protein produced.

Single nucleotide polymorphism (SNP)

Single base change present in at least 1 % of a population; the most common form of genetic variation.

Polymorphism

A DNA variant that exists at a frequency of ≥1 % in a population and is usually non-deleterious.

Mutation rate

Frequency at which new DNA sequence changes arise, often expressed as mutations per cell division or per base replicated.

Transition mutation

Point mutation replacing a purine with another purine (A↔G) or a pyrimidine with another pyrimidine (C↔T).

Transversion mutation

Point mutation replacing a purine with a pyrimidine or vice versa (A/G ↔ C/T).

Frameshift mutation

Insertion or deletion of bases not divisible by three that shifts the reading frame of a coding sequence.

Insertion mutation

Addition of one or more nucleotides into DNA; can disrupt the reading frame or add extra amino acids.

Deletion mutation

Loss of one or more nucleotides from DNA; can remove amino acids or shift the reading frame.

Transposon

Mobile DNA element that can move to new genomic locations, often inserting mutations; “jumping gene.”

Point mutation

Alteration affecting a single nucleotide pair in DNA.

Multisite mutation

Change that affects two or more consecutive bases, ranging from a few nucleotides to large genomic segments.

Phenylketonuria (PKU)

Autosomal recessive disorder caused by PAH gene mutations leading to toxic phenylalanine accumulation and intellectual disability.

Phenylalanine hydroxylase (PAH) gene

Gene on chromosome 12 that encodes the enzyme converting phenylalanine to tyrosine; mutations cause PKU.

Sickle cell disease

Autosomal recessive blood disorder caused by a missense mutation in HBB that produces abnormal haemoglobin S and deformed red cells.

Thalassaemia

Group of inherited disorders with reduced or absent haemoglobin chains, often due to nonsense or other mutations, leading to severe anaemia.

Proto-oncogene

Normal gene that promotes cell growth/division; gain-of-function mutations convert it to an oncogene.

Tumour-suppressor gene

Gene that restrains cell proliferation; loss-of-function mutations remove this brake and predispose to cancer.

Caretaker gene

Gene whose product maintains genomic stability through DNA repair; mutations increase overall mutation rates.

BRCA1

Tumour-suppressor gene involved in double-strand break repair; germline mutations greatly increase breast and ovarian cancer risk.

BRCA2

Tumour-suppressor gene distinct from BRCA1 but also involved in homologous recombination repair; mutations predispose to breast, prostate and other cancers.

BRAF

Proto-oncogene encoding a serine/threonine kinase; activating mutations (e.g., V600E) drive melanoma and other cancers.

Tautomeric shift

Spontaneous rearrangement of protons in DNA bases to rare forms that mispair during replication, creating spontaneous mutations.

Base analogue

Chemical that resembles a normal DNA base and can be incorporated into DNA, increasing mispairing and mutation rates.

5-Bromouracil (5-BU)

Thymine base analogue; keto form pairs with A, enol form pairs with G, causing A→G transitions.

2-Aminopurine (2-AP)

Adenine analogue; shifts to mispair with C, leading to T→C transitions.

Deamination

Removal of an amino group from a base (e.g., cytosine→uracil) often induced by nitrous acid; causes transition mutations.

Alkylation

Addition of alkyl groups (e.g., CH₃) to DNA bases by agents like mustard gas, distorting the helix and leading to mispairing.

Mustard gas

Potent chemical alkylating agent historically used as a weapon; induces DNA cross-links and mutations.

MNNG

N-methyl-N′-nitro-N-nitrosoguanidine, laboratory alkylating mutagen that preferentially modifies guanine in replicating DNA.

Frameshift mutagen

Chemical that intercalates between base pairs and induces single-base insertions or deletions.

Acridine dye

Planar intercalating molecule (e.g., proflavine) that causes frameshift mutations; found in cigarette smoke and used experimentally.

Thymine dimer

UV-induced covalent linkage between adjacent thymines, distorting DNA and blocking replication.

Ultraviolet (UV) radiation

Non-ionising physical mutagen (max effect 260 nm) that induces thymine dimers and skin cancer.

Alpha radiation

Low-penetrance, high-energy particle emission (e.g., from radon) that can cause DNA damage when inhaled or ingested.

Beta radiation

Moderate-penetrance emission of electrons (e.g., 32P) that can incorporate into DNA and cause mutations.

Gamma radiation

Highly penetrating electromagnetic radiation that causes double-strand breaks and chromosomal damage.

Photolyase

Light-activated enzyme that directly breaks thymine dimers, restoring DNA without cutting the backbone.

DNA glycosylase

Enzyme initiating base excision repair by removing abnormal or damaged bases and creating an AP site.

DNA methyltransferase (repair)

Enzyme that transfers aberrant methyl/ethyl groups from damaged bases to itself, directly reversing alkylation damage.

AP site

Location in DNA missing a purine or pyrimidine base after glycosylase action; substrate for AP endonuclease.

Endonuclease

Enzyme that cleaves phosphodiester bonds within a DNA strand, as in excision repair of damaged regions.

Nick translation

DNA polymerase-mediated process where 5′→3′ exonuclease removes nucleotides ahead of a nick while adding new ones behind it.

Proofreading (DNA polymerase)

3′→5′ exonuclease activity of DNA polymerase that removes misincorporated bases during replication, lowering mutation rate.

RecA protein

Bacterial recombinase that mediates strand exchange during post-replication repair and the SOS response.

SOS response

Bacterial emergency DNA-damage response that allows error-prone replication across lesions by suspending proofreading.

Suppressor mutation

Second mutation that compensates for or masks the effect of a primary mutation, restoring phenotype.

Intragenic suppression

Second mutation within the same gene (e.g., opposite frameshift) that restores correct reading frame.

Intergenic suppression

Second mutation in a different gene (often tRNA anticodon change) that counteracts an initial mutation.

Base excision repair

Pathway that removes a damaged base via glycosylase, cuts the backbone, fills the gap and ligates the strand.

Newborn blood spot screening

UK programme using heel-prick blood to detect nine serious inherited conditions (e.g., PKU, CF, SCD) early in life.