Table 1.
Ubiquitin family- and proteasome-target proteins involved in DNA repair (post-translational regulation)
| Target protein | DNA repair pathway | Modifier | Result |
|---|---|---|---|
| MGMT | DR | Poly-ubiquitin & 26S proteasome | Degradation |
| hMutSa complex (MSH2/MSH6) | MMR | Poly-ubiquitin & 26S proteasome | Degradation |
| NEDD8 | Unknown | ||
| hEXO1b | MMR | Poly-ubiquitin & 26S proteasome | Degradation |
| TDG | BER | Poly-ubiquitin & 26S proteasome | Degradation |
| SUMO | Release from DNA | ||
| UNG2 | BER | Poly-ubiquitin & 26S proteasome | Degradation |
| PARP-1 | BER | Poly-ubiquitin | Degradation |
| 26S proteasome | |||
| Ubc9/SUMO | Deceleration of DNA synthesis for DNA repair prior to replication | ||
| XRCC1 | BER | SUMO | Unknown |
| XPC | NER | Poly-ubiquitin | Increased DNA-binding |
| 26S proteasome | Degradation | ||
| SUMO | Stabilisation | ||
| HR23 | NER | 26S proteasome | Binding to 26S proteasome, inhibition of XPC |
| 19S proteasome | Multi-ubiquitylation | ||
| DDB2 | NER | Poly-ubiquitin & 26S proteasome | Degradation |
| Rad51 | HR | Poly-ubiquitin & 26S proteasome | Degradation |
| 19S proteasome (DSS1) | Rad51 focus formation, binding at DNA-damage site | ||
| SUMO | Nuclear trafficking | ||
| NEDD8 | Unknown | ||
| Rad52 | HR | SUMO | Protection from degradation, accumulation after DNA damage |
| Ku70 | NHEJ | Poly-ubiquitin & 26S proteasome | Degradation |
| Ku80 | NHEJ | Poly-ubiquitin & 26S proteasome | Degradation |
| SUMO | Unknown | ||
| XRCC4 | NHEJ | Mono-ubiquitin | Lig 4 stabilisation, damage foci & DNA binding, interaction with NHEJ proteins |
| SUMO | Warrants further examination | ||
| DNA PKcs | NHEJ | NEDD8 | Unknown |
| PCNA | TLS | Mono-ubiquitin | Recruitment of TLS polymerases |
| SUMO | HR inhibition, Pol ζ recruitment | ||
| Poly-ubiquitin | Switch to damage avoidance sub-pathway | ||
| Rad18 | TLS | Poly-ubiquitin & 26S proteasome | Degradation |
| Mono-ubiquitin | Equilibration between nuclear and cytoplasmic protein levels | ||
| Pol η | TLS | Poly-ubiquitin & 26S proteasome | Degradation |
| Pol δ, ɛ, ζ | NEDD8 | Unknown | |
| p12 subunit of Pol δ | MMR, BER, NER, HR | Poly-ubiquitin & 26S proteasome | Degradation |
| p66 subunit of Pol δ | MMR, BER, NER, HR | Mono-ubiquitin | Conformation change (affecting the overall structure & function of the polymerase complex) |
| Poly-ubiquitin | |||
| SUMO | |||
| FANCC | FA | Poly-ubiquitin & 26S proteasome | Degradation |
| FANCD2 | FA | Mono-ubiquitin | Interaction with FANCI, chromatin targeting |
| FANCI | FA | Mono-ubiquitin | Interaction with FANCD2, chromatin targeting |
Abbreviations: MGMT, O6-methylguanine-DNA methyltransferase; DR, direct repair; MSH2, MutS homologue 2; MSH6, MutS homologue 6; MMR, mismatch-repair; NEDD8, neural precursor cell expressed developmentally down-regulated 8; hEXO1b, human exonuclease 1b; TDG, thymine-DNA glycosylase; BER, base-excision repair; SUMO, small ubiquitin-like modifier; UNG2, uracil-DNA glycosylase 2; PARP-1, poly-ADP-ribose polymerase; Ubc9, ubiquitin-conjugating enzyme 9; XRCC1, X-ray repair complementing defective repair in Chinese hamster cells 1; XPC, Xeroderma pigmentosum, complementation group C; NER, nucleotide-excision repair; HR23, homologue of Rad23; DDB2, damage-specific DNA binding protein 2; HR, homologous recombination; NHEJ, non-homologous end joining; XRCC4, X-ray repair complementing defective repair in Chinese hamster cells 4; Lig 4, DNA-ligase 4; DNA-PKcs, DNA-dependent protein kinase catalytic subunit; PCNA, proliferating cell nuclear antigen protein; TLS, translesion DNA synthesis; Pol η, DNA polymerase η; Pol δ, ɛ, ζ, DNA polymerases δ, ɛ, ζ; FANCC, Fanconi anaemia, complementation group C; FANCD2, Fanconi anaemia complementation group D2; FANCI, Fanconi anaemia complementation group I.