Mismatch repair, BER/NER, double-strand-break repair (HR, NHEJ), homologous recombination.
Dna Repair And Recombination
DNA damage
Endogenous (hydrolysis, oxidation, alkylation, replication errors) or exogenous (UV, ionising radiation, chemical mutagens) lesions.…
Mismatch repair (MMR)
Post-replicative correction of base-base mismatches and small indels. MutSα/β recognise lesion; MutLα nicks daughter strand; EXO1 excises;…
Base excision repair (BER)
Lesion-specific DNA glycosylase removes damaged base (8-oxo-G, uracil, alkylated base) creating AP site → AP endonuclease → gap-fill by Pol…
Nucleotide excision repair (NER)
Repairs bulky/helix-distorting lesions (UV pyrimidine dimers, chemical adducts). XPC or CSB recognises, TFIIH unwinds, XPF/XPG excise…
Homologous recombination (HR)
Error-free double-strand break repair using sister chromatid as template. End resection by MRN + CtIP → RAD51 filament → strand invasion →…
Non-homologous end joining (NHEJ)
Error-prone DSB repair via direct ligation of broken ends. Ku70/80 + DNA-PKcs + Artemis + XRCC4/LigIV. Active throughout cell cycle;…
DNA double-strand break (DSB)
Most cytotoxic DNA lesion: both strands severed. Sensed by MRN complex; γH2AX phosphorylation marks chromatin. Repaired by HR (S/G2) or…
Direct reversal repair
Single-enzyme reversal of specific lesions: photolyase reverses pyrimidine dimers; MGMT removes O6-methylguanine alkyl groups. No excision…
Translesion DNA synthesis
Y-family polymerases (Polη, Polκ, Polι, Rev1) bypass bulky lesions during replication at cost of accuracy. Essential for UV damage…
BRCA/Fanconi anemia pathway
BRCA1/BRCA2 + FA core complex coordinate HR repair of interstrand crosslinks. Germline mutations predispose to breast/ovarian cancer;…
Double-strand-break repair pathway-choice framework
DSBs repaired by two competing pathways: (1) Non-homologous end joining (NHEJ; Ku70/80 + DNA-PKcs + LIG4): fast, error-prone, active…
Mismatch-repair (MMR) framework
MutS/MutL → MSH2/MSH6 + MLH1/PMS2 in eukaryotes: post-replicative recognition of base-pair mismatches and small (1-3 nt) insertion/deletion…
Nucleotide excision repair (NER)
Setlow 1964 + Sancar 1983 NER: XPC + XPA + ERCC1-XPF + XPG + RFC excise 24-32 nt around bulky lesions (UV CPD/6-4PP); GG-NER + TC-NER…
Base excision repair (Lindahl 1974)
Lindahl 1974 (Nobel 2015) BER: glycosylase removes damaged base; AP-endonuclease cleaves; DNA pol-beta + Lig-3 short-patch (1 nt) or…
Homologous recombination (Rad51-BRCA)
Petes-Stahl 1979 + Rothstein 1983 HR: MRN complex + CtIP resect; RPA + BRCA2-Rad51 strand-exchange; D-loop + Holliday-junction; BRCA1/2…
NHEJ (Lieber Ku-DNA-PKcs)
Lieber 1990s NHEJ: Ku70/80 + DNA-PKcs synapsis; Artemis nuclease processing; XRCC4-Lig4-XLF ligation; classical NHEJ vs alt-NHEJ MMEJ;…
Mismatch repair (Modrich)
Modrich 1980s (Nobel 2015) MMR: MutS_alpha/_beta detect mismatch; MutL_alpha endonuclease nicks newly-synthesized strand; EXO1 excision +…
Translesion synthesis (Y-family pols)
Friedberg 1990s + Goodman 2002 TLS: damage-tolerance via Y-family polymerases (eta/iota/kappa/Rev1) low-fidelity bypass; eta bypasses CPD;…
XPA-G (Cleaver 1968)
J Cleaver 1968 XP-NER deficiency; modern Sancar-Lindahl-Modrich Nobel 2015 NER + BER + MMR mechanistic foundations.
BRCA1 (King 1990)
M-C King 1990 17q-linkage + Miki 1994 BRCA1 cloning; modern PARP-inhibitor olaparib synthetic-lethality + BRCA-screening.
Recombination (Meselson-Radding 1975)
C Radding-M Meselson 1975 Holliday-junction resolution; modern RecA-RAD51 strand-invasion + crossover-control + HR pathway.
DSBR (Szostak 1983)
J Szostak 1983 (Nobel 2009) DSBR double-strand-break-repair; modern synthesis-dependent-strand-annealing SDSA + BIR.
MMR (Modrich 2015)
P Modrich 2015 (Nobel 2015) MMR mismatch-repair; modern Lynch-syndrome MSI + 2017 dMMR-Keytruda first-tissue-agnostic.
CRISPR-Cas9 (Doudna 2012)
J Doudna-E Charpentier 2012 (Nobel 2020) CRISPR-Cas9 in vitro; modern prime-editing Anzalone 2019 + base-editing 2024.