DNA mutations and repair CH 8

Germ-line mutations

Mutations that occur in gametes or gamete precursor cells, are transmitted to subsequent generations, and provide the raw material for natural selection.

Somatic mutations

Mutations occurring in non-germline body cells that are not passed on to offspring, but can affect individual survival and lead to cancer.

Luria-Delbrück fluctuation experiment

A classic 1943 bacterial test demonstrating that genetic mutations arise spontaneously prior to bactericide exposure rather than as an induced response to the selective agent.

Transition mutation

A point mutation substitution where a purine is replaced by another purine, or a pyrimidine is replaced by another pyrimidine.

Transversion mutation

A point mutation substitution where a purine is replaced by a pyrimidine, or a pyrimidine is replaced by a purine.

Depurination

A form of spontaneous DNA damage occurring roughly 10,000 times per cell per day in which the glycosidic bond hydrolyzes, releasing an adenine or guanine base.

Deamination of cytosine

The spontaneous removal of an amine group that converts cytosine to uracil, creating a transition mutation from a C-GC-G base pair to an A-TA-T base pair after replication.

Thymine dimer

A lesion formed when ultraviolet (UV) radiation induces abnormal covalent bonds between adjacent thymine bases on the same DNA strand.

Proofreading function of DNA polymerase

A 3′-to-5′ exonuclease activity that recognizes mispaired nucleotides at the growing end of DNA and excises them during replication.

Base analog

A chemical mutagen with a structure nearly identical to a standard nitrogenous base (such as 5-bromouracil) that incorporates into DNA and causes base mispairing during replication.

Intercalating agent

A mutagenic chemical (such as proflavin) that slips between stacked base pairs of the double helix, causing single base-pair insertions or deletions.

Base excision repair (BER)

A DNA repair mechanism that uses specific DNA glycosylases to remove an altered base (such as uracil), followed by endonuclease cleavage, gap synthesis, and ligation.

Nucleotide excision repair (NER)

A multi-protein repair pathway (utilizing UvrA, UvrB, and UvrC in bacteria) that recognizes helix-distorting damage like thymine dimers and excises an oligonucleotide containing the lesion.

Xeroderma pigmentosum

A hereditary human condition caused by defects in nucleotide excision repair genes, characterized by extreme sensitivity to sunlight and high rates of skin cancer.

Non-homologous end joining (NHEJ)

A double-strand break repair pathway in which proteins like Ku70 and Ku80 bind exposed DNA ends and directly ligate them without requiring a homologous template.

Methyl-directed mismatch repair

A bacterial replication error correction pathway that differentiates parental strands via methyl tags, using MutS, MutL, and MutH to excise misincorporated bases on the unmethylated daughter strand.

Hydroxylating agent

A chemical mutagen (such as hydroxylamine) that adds an −OH−OH group to cytosine, causing it to mispair with adenine and leading to a C-G→T-AC-G→T-A transition mutation.

Alkylating agent

A chemical mutagen (such as ethylmethane sulfonate) that adds an ethyl or methyl group to a base, causing altered pairing such as modified guanine pairing with thymine to produce a G-C→A-TG-C→A-T transition.

Deaminating agent

A chemical mutagen (such as nitrous acid) that removes amino (−NH2−NH2​) groups, converting cytosine to uracil or adenine to hypoxanthine and resulting in transition mutations.

Oxidative DNA damage

Natural DNA damage caused by reactive oxygen species that oxidizes guanine into 8-oxodG, which mispairs with adenine and results in a G-C→T-AG-C→T-A transversion after replication.

X-ray induced DNA damage

Double-strand breaks caused when ionizing radiation cleaves the phosphodiester sugar-phosphate backbone of DNA, potentially causing deletions and large chromosomal rearrangements.

Base tautomerization

A spontaneous shift of hydrogen atoms that temporarily converts standard nitrogenous bases into rare enol or imino isomers, resulting in mispairing and point mutations during DNA replication.

Homologous recombination (HR)

A high-fidelity, homology-dependent repair pathway for double-strand breaks (mediated by proteins such as BRCA1 and BRCA2) that uses an undamaged homologous sister chromatid as a template to direct repair synthesis.

DNA glycosylase

An enzyme in base excision repair (BER) that cleaves the glycosidic bond linking an abnormal base (such as uracil) to deoxyribose, leaving an apurinic or apyrimidinic (AP) site.

AP endonuclease

An enzyme in base excision repair (BER) that cuts the phosphodiester backbone of DNA at an abasic site, initiating excision of the damaged segment.

UvrABC endonuclease

A bacterial nucleotide excision repair protein complex where UvrA and UvrB recognize helix-distorting damage, and UvrB and UvrC cleave the damaged strand on both sides of the lesion.

Paternal age effect on mutation rate

The biological pattern where human sperm carry 2 to 42 to 4 times more mutations than eggs and accumulate more mutations with advancing paternal age, due to continuous mitosis in male germ cells.

Somatic versus germ-line evolutionary impact

Germ-line mutations provide heritable variation that shapes species evolution through natural selection, whereas somatic mutations impact only the individual's survival (such as through oncogenesis) and are not passed to offspring.