DNA Replication, Repair Mechanisms, and Genetic Mutations

Comprehensive vocabulary flashcards covering telomere replication, DNA repair pathways (proofreading, mismatch repair, nucleotide excision repair), associated pathologies such as Xeroderma Pigmentosum, and molecular types of genetic mutations.

Telomere

A repetitive non-coding DNA sequence located at the terminal ends of linear eukaryotic chromosomes (consisting of repeats such as GGG TTA found about $500$ times) that prevents the progressive loss of genetic material during rounds of replication.

Telomerase

A eukaryotic ribonucleoprotein enzyme containing both a protein catalytic subunit and an RNA template ($\text{AAUCCCAUC}$) that synthesizes DNA repeats in the $5'$ to $3'$ direction to extend the ends of chromosomes.

Elizabeth Blackburn

The scientist and $2009$ Nobel Laureate who discovered the mechanism of how telomeres and the enzyme telomerase function to protect chromosome ends.

Telomere Replication

The multi-step process in eukaryotes where telomerase binds to the unreplicated $3'$ overhang and extends the template strand using its intrinsic RNA template, enabling primase and DNA polymerase to complete synthesis of the lagging strand.

Proofreading

The primary DNA repair mechanism occurring during DNA replication in which DNA polymerase identifies an incorrect base pair, stops synthesis, backs up to excise the mismatched nucleotide, and inserts the correct base.

$3'$ Exonuclease Activity

The specific enzymatic function of DNA polymerase (such as DNA Polymerase III in prokaryotes) that enables it to reverse direction and cleave an incorrectly paired nucleotide from the $3'$ end of the growing daughter strand.

Methylation

The covalent addition of a methyl group ($-\text{CH}_3$) to specific bases on the parental DNA strand, allowing mismatch repair enzymes to distinguish the original template strand from the newly synthesized, unmethylated strand.

Mismatch Repair

A repair mechanism operating after replication in which nuclease cleaves a phosphodiester bond on the unmethylated daughter strand, DNA polymerase excises and replaces the mispaired base, and DNA ligase seals the nick.

Nuclease

An enzyme that cleaves phosphodiester bonds between nucleotides in nucleic acids; it nicks the nascent strand in mismatch repair and cuts on both sides of a damaged site in nucleotide excision repair.

DNA Ligase

The enzyme responsible for sealing gaps in the sugar-phosphate backbone by catalyzing the formation of the final phosphodiester bond between adjacent nucleotides.

Pyrimidine Dimer

A DNA lesion formed when adjacent pyrimidines on the same strand (such as thymine-thymine, cytosine-cytosine, or cytosine-thymine) become covalently bonded together following exposure to ultraviolet (UV) radiation.

Nucleotide Excision Repair

A repair pathway that removes bulky lesions such as pyrimidine dimers; nuclease cuts roughly $10$ bases around the dimer (about $5$ bases on one side and $3$ bases on the other), helicase unwinds and removes the damaged segment, DNA polymerase fills the gap, and DNA ligase seals the nick.

Xeroderma Pigmentosum

A genetic disorder characterized by nonfunctional nucleotide excision repair enzymes that fail to correct UV-induced thymine dimers, resulting in severe skin lesions, photosensitivity, and an increased risk of skin cancer.

Spontaneous Mutation

A genetic sequence alteration that occurs naturally without external intervention, typically arising from uncorrected errors made by DNA polymerase during replication or internal metabolic reactions.

Induced Mutation

A permanent change in DNA sequence caused by external environmental agents or mutagens, such as ultraviolet (UV) light, X-rays, radiation, or reactive chemicals.

Point Mutation

A mutation that occurs when a single nucleotide base pair in DNA is replaced or substituted with a different base pair.

Silent Mutation

A point substitution mutation in which a change in a DNA nucleotide does not alter the encoded amino acid sequence of the resulting polypeptide.

Missense Mutation

A point substitution mutation in which a single base substitution alters a codon to specify a different amino acid in the protein sequence.

Nonsense Mutation

A point substitution mutation that alters an amino acid-encoding codon into a premature stop codon, leading to truncated protein products that are often nonfunctional and targeted for proteasomal degradation.

Frameshift Mutation

A mutation resulting from the insertion or deletion of nucleotides not in multiples of three, which shifts the triplet reading frame of the mRNA during translation and alters the downstream amino acid sequence.