DNA Damage and Repair

Vocabulary flashcards covering key terms and definitions from the lecture notes on DNA damage and repair.

Depurination

Spontaneous loss of a purine base (A or G) from DNA due to hydrolysis of the bond to deoxyribose.

Deamination

Conversion of cytosine to uracil in DNA, potentially leading to a C→T transition if unrepaired.

Bulky lesions

Large covalent linkages between adjacent nucleotides that distort the DNA helix and interfere with replication.

Copy errors

Incorrect base incorporation by DNA polymerase during replication.

Mutagen

An agent (physical or chemical) that can alter DNA structure or sequence.

Base analogs

Chemical mutagens that resemble purines/pyrimidines and may be incorporated into DNA during replication.

Intercalating agents

Molecules that insert between base pairs, distorting the helix and causing misincorporation during replication.

Direct acting agents

Mutagens that chemically react directly with DNA to cause damage.

Indirect acting agents

Mutagens that require metabolic activation (often via cytochrome P-450) to damage DNA.

UV radiation

Physical mutagen with UV-A, UV-B, and UV-C subtypes; energy can damage DNA.

UV-A

Induces oxidative damage and can cause double-strand breaks in DNA.

UV-B

Induces cyclobutane pyrimidine dimers (C–C or T–T) between adjacent pyrimidines.

UV-C

Germicidal UV; highly energetic but largely filtered by the ozone layer.

Ionizing radiation

Radiation that ionizes molecules, creating radicals; includes X-rays, gamma rays, and particulate forms.

X-rays

Electromagnetic ionizing radiation used in imaging and therapy.

Gamma rays

High-energy electromagnetic ionizing radiation.

Alpha particles

Helium nuclei; a type of particulate ionizing radiation.

Beta particles

High-speed electrons emitted by radioactive decay.

DNA damage from ionizing radiation

Single-strand breaks, double-strand breaks, base damage, and cross-linking.

DNA Repair

Correction of accidental DNA lesions; involves damage reversal, removal, or tolerance.

Damage reversal

Repair mechanisms that restore the original DNA chemistry without removing bases.

Damage removal

Removal of damaged bases or nucleotides followed by synthesis to fill gaps.

Damage tolerance

Replication past lesions with specialized polymerases that bypass damage.

Base Excision Repair (BER)

Repair of small, non-bulky lesions via DNA glycosylases, AP endonuclease, polymerase, and ligase.

DNA glycosylases

Enzymes that recognize damaged bases, flip them out, and excise them from DNA.

AP endonuclease

Enzyme that cuts the DNA backbone at an apurinic/apyrimidinic site to create a gap.

Nucleotide Excision Repair (NER)

Repair of bulky lesions via a multisubunit complex, excision of a damaged strand segment, then synthesis and ligation.

DNA Helicase (in NER context)

Enzyme that unwinds DNA around a bulky lesion to allow removal of the damaged strand segment.

DNA polymerase

Enzyme that fills in gaps with new nucleotides during BER/NER/MMR.

DNA ligase

Enzyme that seals nicks in the DNA backbone after repair synthesis.

Mismatch Repair (MMR)

Correction of replication-induced base mismatches; MutS/MutL recognize mismatches and direct excision.

MutS

Protein that detects base-base mismatches during MMR.

MutL

Protein that partners with MutS to coordinate excision in MMR.

Proofreading

3'→5' exonuclease activity of replicative DNA polymerases; detects and removes mispaired bases.

Back-up polymerases

Additional, often error-prone polymerases used when replication stalls; provide extension with lower fidelity.

Transcription-coupled Repair (TCR)

Repair pathway that prioritizes active genes; RNA Pol II stalls at lesions and recruits repair factors (CSB, TFIIH, XPG).

CSB

Cockayne syndrome B protein; recognizes stalled RNA polymerase II to initiate TCR.

TFIIH

Transcription factor II H; remodels RNA Pol II and participates in repair processes.

XPG

Endonuclease that makes cuts during NER/TCR to remove damaged DNA.

Double-strand breaks (DSBs)

Breaks spanning both DNA strands; repaired by NHEJ or homologous recombination.

Nonhomologous End Joining (NHEJ)

Direct ligation of broken ends; Ku70/80 bind ends, DNA-PK is recruited, ends are processed and ligated, often with small deletions.

Ku70/80

Protein heterodimer that binds DNA ends to initiate NHEJ.

DNA-PK

DNA-dependent protein kinase; activates processing and ligation steps during NHEJ.

Homologous Recombination (HR)

Accurate DSB repair using a sister chromatid as template; ends processed to 3' overhangs; Rad51 mediates strand invasion; a holiday junction forms and is resolved.

Rad51

Recombinase that promotes pairing of 3' overhangs with the sister chromatid in HR.

Holiday junction

Four-way DNA structure formed during HR; resolved to produce recombinant sequences.

ATM

Kinase activated by DNA damage; phosphorylates targets to activate cell cycle arrest and repair pathways.

p53

Tumor suppressor protein activated by ATM; induces transcription of p21 and other targets to pause the cell cycle.

Mdm2

Regulator that targets p53 for degradation; activity modulated by p53 phosphorylation.

p21

CDK inhibitor induced by p53; blocks G1/S and S-Cdk activity to enforce cell cycle arrest.

XPG

Endonuclease that makes cuts during NER/TCR to remove damaged DNA.

Chk1

Checkpoint kinase that helps enforce cell cycle arrest by inhibiting Cdk activation.

Chk2

Checkpoint kinase that contributes to cell cycle arrest in response to DNA damage.