Table 3.
The major steps and protein participants in global genome and transcription-coupled NER. Only the recognition step differs between these two sub-pathways of NER.
NER STEP | PROTEIN | BIOCHEMICAL ACTIVITY | SUBSTRATE | |
---|---|---|---|---|
RECOGNITION | GLOBAL GENOME | XPC/RAD23B | DNA Binding/TFIIH recruitment | DNA helix distortion |
DDB1/DDB2 (XPE) | DNA Binding | UV-damaged DNA | ||
XPA | DNA Binding | XPC-TFIIH bound DNA | ||
TRANSCRIPTION COUPLED | CSA | Unknown/Part of ubiquitin ligase complex | Stalled RNA Pol | |
CSB | DNA-dependent ATPase | Stalled RNA Pol | ||
DNA UNWINDING (TFIIH Multisubunit Complex*) | XPB (ERCC3) | 3′ to 5′ DNA helicase/ATPase | ||
XPD (ERCC2) | 5′ to 3′ DNA helicase/ATPase | |||
INCISION | XPG (ERCC5) | 3′-Incision | 5′-Flap, Bubble | |
ERCC1/XPF (ERCC4) | 5′-Incision complex (catalyzed by XPF) | 3′-Flap, Bubble | ||
POLYMERIZATION | POLδ (POLε) | PCNA-dependent replicative polymerase(s) | DNA gap (~25–30 nt) | |
LIGATION | LIG1 | Ligase | DNA nick | |
XRCC1/LIG3α | Ligase complex | DNA nick |
Of the multiple subunits that comprise the TFIIH transcription complex, only XPB and XPD are listed here. RPA (not listed) participates in NER by binding and protecting the single-stranded DNA regions generated upon duplex unwinding.