| Category | Summary |
|---|---|
| Identity/domains | Human DDB2 is the DNA damage-binding protein 2 encoded by **DDB2** (UniProt Q92466), a WD40-family protein that contains an N-terminal helix-loop-helix region for DDB1 association and a 7-bladed WD40 β-propeller that mediates DNA binding; DDB2 is unstable/poorly soluble without DDB1. (pqac-00000000, pqac-00000004) |
| Core molecular function | DDB2 is the lesion-recognition subunit of the UV-DDB complex and acts early in global-genome nucleotide excision repair (GG-NER) by binding UV-damaged DNA and facilitating recruitment/transfer to XPC, especially for lesions that XPC recognizes inefficiently on its own. (pqac-00000005, pqac-00000006, pqac-00000007) |
| Lesion specificity | DDB2 binds strongly to UV photolesions, particularly 6-4 photoproducts and also CPDs; reported substrates additionally include abasic/AP sites, mismatches, and compound lesions. Structural work showed recognition of a 6-4PP and an abasic-site mimic (THF). (pqac-00000000, pqac-00000002, pqac-00000004, pqac-00000006) |
| Key complexes/partners | DDB2 forms a heterodimer with DDB1 (UV-DDB) and serves as the substrate receptor in the CRL4^DDB2 ubiquitin ligase with CUL4A/RBX1; functionally important partners include XPC, centrin-2, COP9 signalosome, PARP1, p97 segregase, and chromatin substrates such as histones. (pqac-00000000, pqac-00000002, pqac-00000003, pqac-00000005) |
| Post-translational regulation | UV-damage binding activates CRL4^DDB2-dependent ubiquitination of DDB2, XPC, and histones; mono-ubiquitination can be compatible with damage binding, whereas poly-ubiquitination abrogates DDB2 damaged-DNA binding and promotes proteasomal degradation. XPC competitively suppresses DDB2 ubiquitination and stabilizes endogenous DDB2 after UV; regulation also involves COP9/neddylation, p38 MAPK, and PARP1-mediated stabilization. (pqac-00000002, pqac-00000003, pqac-00000005) |
| Cellular localization | DDB2 functions primarily in the nucleus on UV-damaged chromatin, where it rapidly translocates after UV exposure, binds lesions ahead of XPC, and accumulates at chromatin-associated repair sites. (pqac-00000004, pqac-00000007) |
| Pathways | DDB2 operates in global-genome NER, coupling lesion detection to chromatin remodeling and ubiquitin signaling; its activity promotes lesion handoff to XPC and helps organize repair in accessible chromatin regions. Recent PDAC work also links DDB2 to ionizing-radiation responses via checkpoint signaling and PARP1-associated DSB repair processes. (pqac-00000001, pqac-00000007, pqac-00000009, pqac-00000011) |
| 2023-2024 developments | Recent studies expand DDB2 biology beyond canonical UV repair: in PDAC, higher DDB2 promoted radioresistance, Chk1/Chk2 phosphorylation, PARP1 activity, and reduced residual γH2AX after irradiation; in tumor-biology models, reduced or altered DDB2 regulation was linked to EMT/NF-κB programs and metastasis-associated phenotypes. (pqac-00000008, pqac-00000009, pqac-00000010, pqac-00000012, pqac-00000013) |
| Applications/biomarkers | DDB2 is being investigated as a predictive biomarker for radiotherapy response and olaparib radiosensitization in PDAC, and as a protein biomarker in radiation biodosimetry assays; recent cancer studies also support its relevance as a metastasis/EMT-associated regulatory node in some tumor contexts. (pqac-00000008, pqac-00000009) |
| Quantitative stats | Structural studies reported DDB2-induced ~40° DNA kinking, ~2100 Ų DNA-contact surface, and ~3900 Ų DDB1-DDB2 interface; one mechanistic model reported ~90% of 6-4PPs in MNase-sensitive chromatin and ~75% removed within 1 h in wild-type cells, with ~50% CPD excision efficiency in XP-E settings. In a 2024 biodosimetry assay using DDB2+BAX, classification accuracy was 97.92% in human and 96% in NHP blood, with dose-prediction R² values of 0.79 and 0.80, respectively. (pqac-00000000, pqac-00000001, pqac-00000004) |


*Table: This table summarizes the evidence-backed functional annotation of human DDB2 (UniProt Q92466), covering its identity, molecular role in GG-NER, regulation, recent 2023-2024 developments, and emerging biomarker applications. It is useful as a compact reference linking each claim to specific retrieved evidence contexts.*