Table 1. Major DNA Repair Pathways, Main Substrates and Biochemical Steps, and Participating Proteins.
For further information and a more expansive list of the DDR proteins, please visit: https://www.mdanderson.org/documents/Labs/Wood-Laboratory/human-dna-repair-genes.html.
| DNA Repair Pathway Specific Biochemical Step |
Main Substrate(s) | Primary Protein(s) (Sub-Pathway) |
|---|---|---|
| Direct Reversal (DR) | ||
| Direct Transfer (to active site cysteine) | Methylated bases (e.g., O6-MeG) | MGMT |
| Direct Removal (via a-ketoglutarate-dependent reaction) | Alkylated bases (e.g., 1-MeA, 3-EtA, 3-MeC), certain ethenoadducts | ALKBH2, ALKBH3 |
| Mismatch Repair (MMR) | ||
| Recognition | Base-base mismatch, small insertion/deletion (INDEL) | MSH2/MSH6 (a.k.a., MUTSα) |
| Small and larger (~10 nt) INDEL | MSH2/MSH3 (a.k.a., MUTSβ) | |
| Incision | Leading Strand | MLH1/PMS2 (a.k.a., MUTLα) |
| Excision | 5′-Nick | EXO1 (EXO1-dependent) |
| 3′-Nick | MUTLα, POLδ (EXO1-independent) | |
| DNA Synthesis | Large Gap | POLδ |
| Ligation | Nick | LIG1 |
| Base Excision Repair (BER) | ||
| Base Excision | Uracil | UDG, SMUG1 |
| Oxidized Base | OGG1, MUTYH, NTH1, NEIL1, NEIL2, NEIL3 | |
| Alkylated Base | MPG | |
| Mismatched Base | TDG, MBD4 | |
| AP Site Incision | AP Site | APE1, AP Lyase |
| Termini Clean-Up (also part of single-strand break repair) | 5′-deoxyribose phosphate | POLβ |
| 3′-α,β-polyunsaturated aldehyde | APE1 | |
| 3′-phosphate | PNKP (APE1-independent) | |
| 3′-topoisomerase 1 adduct | TDP1 | |
| 5′-adenylate | APTX | |
| 5′-Flap (product of Long-patch BER) | FEN1 | |
| Non-enzymatic scaffold protein | XRCC1 | |
| DNA Synthesis | Single Nucleotide Gap | Short-patch (SP) BER: POLβ |
| Gap with Obstructive 5′-Terminus | Long-patch (LP) BER: POLε or POLδ | |
| Ligation | Nick | XRCC1/LIG3α or LIG1 (mainly LP-BER) |
| Nucleotide Excision Repair (NER) | ||
| Recognition & Repair Initiation | Helix-distorting Lesion | Global Genome (GG-NER): XPC/RAD23B, XPE/DDB2 |
| Transcription-blocking Lesion; Stalled RNAPII | Transcription-Coupled (TC-NER): CSB, CSA | |
| Damage Verification & Helix Unwinding | Initiating NER Complex | XPA, RPA, TFIIH |
| Damage Excision | Bubble Structure | XPG (3′ incision), ERCC1/XPF (5′ incision) |
| DNA Synthesis | Gap | POLδ |
| Ligation | Nick | LIG1 (replicating cells), LIG3 (non-replicating cells) |
| Non-Homologous End-Joining (NHEJ) | ||
| Recognition & Signaling | Two-Ended Double-strand Break (DSB) | KU70/KU80, DNA-PKcs |
| End Processing | DSB End | Artemis, POLλ, POLμ, TdT (see Termini Clean-Up as well) |
| End-Joining Ligation | Compatible Ends | XLF, XRCC4, LIG4 |
| Homologous Recombination (HR) | ||
| Recognition & Signaling | Two-Ended or One-Ended (collapsed replication fork) DSB | MRN (MRE11/RAD50/NBS1) complex, ATM, RBBP8 |
| Long-Range Resection | DSB End | EXO1, DNA2, BLM |
| Strand Exchange | Single-stranded Resection Products | RAD51, RAD51 paralogs, BRCA2, RAD54 |
| DNA Synthesis | Exchange Primer-Template | POLε, POLδ, POLκ, POLη |
| Holliday Junction Resolution | Cross-Shape Recombination Intermediate | TOPO3α/BLM, GEN1, MUS81/EME1, SLX1/SLX4 |
| Ligation | Nick | LIG1 |