DNA excision repair protein ERCC-8 (Cockayne syndrome WD repeat protein CSA)
1_MLGFL 6_ SARQT 11_ GLEDP 16_ LRLRR 21_ AESTR 26_ RVLGL 31_ ELNKD 36_ RDVER 41_ IHGGG 46_ INTLD 51_ IEPVE 56_ GRYML 61_ SGGSD 66_ GVIVL 71_ YDLEN 76_ SSRQS 81_ YYTCK 86_ AVCSI 91_ GRDHP 96_ DVHRY 101_ SVETV 106_ QWYPH 111_ DTGMF 116_ TSSSF 121_ DKTLK 126_ VWDTN 131_ TLQTA 136_ DVFNF 141_ EETVY 146_ SHHMS 151_ PVSTK 156_ HCLVA 161_ VGTRG 166_ PKVQL 171_ CDLKS 176_ GSCSH 181_ ILQGH 186_ RQEIL 191_ AVSWS 196_ PRYDY 201_ ILATA 206_ SADSR 211_ VKLWD 216_ VRRAS 221_ GCLIT 226_ LDQHN 231_ GKKSQ 236_ AVESA 241_ NTAHN 246_ GKVNG 251_ LCFTS 256_ DGLHL 261_ LTVGT 266_ DNRMR 271_ LWNSS 276_ NGENT 281_ LVNYG 286_ KVCNN 291_ SKKGL 296_ KFTVS 301_ CGCSS 306_ EFVFV 311_ PYGST 316_ IAVYT 321_ VYSGE 326_ QITML 331_ KGHYK 336_ TVDCC 341_ VFQSN 346_ FQELY 351_ SGSRD 356_ CNILA 361_ WVPSL 366_ YEPVP 371_ DDDET 376_ TTKSQ 381_ LNPAF 386_ EDAWS 391_SSDEE
1: Substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in transcription-coupled nucleotide excision repair (TC-NER), a process during which RNA polymerase II-blocking lesions are rapidly removed from the transcribed strand of active genes (PubMed:12732143, PubMed:16751180, PubMed:16964240, PubMed:32142649, PubMed:34526721, PubMed:38316879, PubMed:38600235, PubMed:38600236). Following recruitment to lesion-stalled RNA polymerase II (Pol II), the CSA complex mediates ubiquitination of Pol II subunit POLR2A/RPB1 at 'Lys-1268', a critical TC-NER checkpoint, governing RNA Pol II stability and initiating DNA damage excision by TFIIH recruitment (PubMed:12732143, PubMed:16751180, PubMed:16964240, PubMed:32142649, PubMed:32355176, PubMed:34526721, PubMed:38316879, PubMed:38600235, PubMed:38600236). The CSA complex also promotes the ubiquitination and subsequent proteasomal degradation of ERCC6/CSB in a UV-dependent manner; ERCC6 degradation is essential for the recovery of RNA synthesis after transcription-coupled repair (PubMed:16751180). Also plays a role in DNA double-strand breaks (DSSBs) repair by non-homologous end joining (NHEJ) (PubMed:29545921)