DNA Damage and Repair - Vocabulary

Vocabulary flashcards covering the key terms related to DNA damage types, mutagens, and repair pathways from the lecture.

Spontaneous DNA lesions

Spontaneous chemical changes in DNA that occur without mutagen exposure, including depurination and deamination.

Depurination

Loss of a purine base from DNA due to hydrolysis of the N-glycosyl bond, creating an abasic (AP) site.

Deamination

Removal of an amino group (e.g., cytosine to uracil) causing a base to mispair during replication.

Bulky lesions

Large DNA lesions that distort the DNA helix (e.g., pyrimidine dimers) and are repaired by nucleotide excision repair.

Pyrimidine dimer

Covalent linkage between adjacent pyrimidines (usually cytosine or thymine) on the same DNA strand, often UV-induced.

Copy errors

Incorrect base incorporation by DNA polymerase during replication, potentially corrected by proofreading and mismatch repair.

DNA polymerase proofreading

3' to 5' exonuclease activity that removes misincorporated nucleotides during replication.

Mutagen

A physical or chemical agent that alters DNA structure or sequence.

Base analogs

Nucleoside/nucleotide analogs that resemble bases and can be incorporated into DNA, often used as antiviral drugs.

Intercalating agents

Chemicals that insert between base pairs, distorting the DNA helix and causing mispairing or frameshifts.

Direct acting mutagens

Chemicals that react directly with DNA without metabolic activation.

Indirect acting mutagens

Chemicals requiring metabolic activation (e.g., by cytochrome P450) to become DNA-reactive.

Non-ionizing radiation

Low-energy radiation (e.g., UVA/UVB) that damages DNA mainly via pyrimidine dimers; less penetrating.

Ionizing radiation

High-energy radiation (e.g., X-rays, gamma rays) or particles that cause breaks and base damage in DNA.

UVA

Long-wavelength UV light that causes oxidative DNA damage and possible double-strand breaks.

UVB

Shorter-wavelength UV light that induces pyrimidine dimers and skin-cancer–associated damage.

UVC

Shortest, most energetic UV light; germicidal but largely filtered by the ozone.

NER (nucleotide excision repair)

Repair pathway for bulky lesions; excises a short DNA segment around the distortion and fills it in.

BER (base excision repair)

Repair pathway for small damaged bases; involves glycosylase, AP endonuclease, polymerase, and ligase.

Glycosylase

Enzyme that recognizes damaged bases and removes them, creating an AP site in BER.

AP endonuclease

Enzyme that cleaves the DNA backbone at an abasic site to initiate BER.

MMR (mismatch repair)

Repair pathway that corrects replication-origin mismatches; uses MutS/MutL in prokaryotes and MSH/MLH in eukaryotes.

MutS/MutL (prokaryotes)

Proteins that recognize mismatches and coordinate mismatch repair in bacteria.

MSH/MLH (eukaryotes)

Homologous counterparts to MutS/MutL that detect and repair base mismatches in eukaryotic cells.

Replicative proofreading

DNA polymerase proofreading during replication; removes misincorporated bases via 3' to 5' exonuclease.

Lesion bypass polymerases

Specialized polymerases with low fidelity that bypass lesions when normal polymerases stall.

TCR (transcription-coupled repair)

Repair pathway that prioritizes actively transcribed genes when RNA Pol II stalls at damage.

CSB

Protein that detects stalled RNA Pol II and helps recruit repair factors in transcription-coupled repair.

TFIIH

Complex that helps unwind DNA and coordinates repair in NER/TCR.

XPG

Endonuclease that makes incisions during NER/TCR to remove the damaged DNA segment.

DSB repair

Repair of double-stranded breaks; main pathways are NHEJ and HR.

NHEJ (non-homologous end joining)

DSB repair that ligates ends without requiring homology; Ku70/80 and DNA-PK drive ligation; error-prone.

Ku70/80

Protein complex that binds DNA ends to initiate NHEJ.

DNA-PK

Kinase complex that promotes end joining in NHEJ.

HR (homologous recombination)

High-fidelity DSB repair using a sister chromatid as a template; favors S/G2 phases.

Rad proteins

Rad51, Rad52, etc.; mediate strand invasion and pairing in HR.

Holliday junction

Four-stranded DNA structure formed during HR that is resolved to yield recombinant DNA.

ATM

Protein kinase activated by DNA damage; phosphorylates CHK1/CHK2 and p53 to coordinate repair.

CHK1/CHK2

Kinases activated by ATM; propagate DNA damage checkpoints and p53 activation.

p53

Tumor suppressor transcription factor activated by DNA damage that induces p21 and can trigger arrest or apoptosis.

p21

CDK inhibitor that halts the cell cycle by inhibiting G1/S and S phase CDKs.

MDM2

Negative regulator of p53; targets p53 for degradation; phosphorylation can modulate this interaction.

Telomere shortening

Progressive loss of chromosome end length leading to p53 activation and growth arrest.

Hayflick limit

Finite number of times a normal somatic cell can divide before senescence.

Endogenous DNA damage

Damage arising from internal cellular sources, such as mitochondrial oxidants.

Exogenous DNA damage

Damage arising from external sources like mutagens, chemicals, or radiation.

Oxidative damage

DNA base modifications caused by reactive oxygen species generated during metabolism or exposure.