DNA excision repair protein ERCC-6
Also known as: CSB, ERCC6
Function
Essential factor 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. Plays a central role in the initiation of the TC-NER process: specifically recognizes and binds RNA polymerase II stalled at a lesion, and mediates recruitment of ERCC8/CSA, initiating DNA damage excision by TFIIH recruitment. Upon DNA-binding, it locally modifies DNA conformation by wrapping the DNA around itself, thereby modifying the interface between stalled RNA polymerase II and DNA. Acts as a chromatin remodeler at DSBs; DNA-dependent ATPase-dependent activity is essential for this function. Plays an important role in regulating the choice of the DNA double-strand breaks (DSBs) repair pathway and G2/M checkpoint activation; DNA-dependent ATPase activity is essential for this function. Regulates the DNA repair pathway choice by inhibiting non-homologous end joining (NHEJ), thereby promoting the homologous recombination (HR)-mediated repair of DSBs during the S/G2 phases of the cell cycle. Mediates the activation of the ATM- and CHEK2-dependent DNA damage responses thus preventing premature entry of cells into mitosis following the induction of DNA DSBs. Remodels chromatin by evicting histones from chromatin flanking DSBs, limiting RIF1 accumulation at DSBs thereby promoting BRCA1-mediated HR. Required for stable recruitment of ELOA and CUL5 to DNA damage sites. Also involved in UV-induced translocation of ERCC8 to the nuclear matrix. Essential for neuronal differentiation and neuritogenesis; regulates transcription and chromatin remodeling activities required during neurogenesis.
Classification
- Family (Pfam)
- PF00271 Helicase_C, PF00176 SNF2-rel_dom, PF25875 WHD_Rad26_CSB
- InterPro
- CC_ERCC-6_N, Helicase_ATP-bd, Helicase_C-like, P-loop_NTPase, SNF2-like_sf, SNF2/RAD54-like_C, SNF2_N, SNF2_RAD54_helicase_repair, WHD_Rad26_CSB-like
- Functional cluster
- DEAD-Box RNA Helicases & Biogenesis Factors
Experimental structures · PDB · 12
- 4CVO X-ray 1.85A
- 7OO3 EM 2.80A
- 7OOB EM 2.70A
- 7OOP EM 2.90A
- 7OPC EM 3.00A
- 7OPD EM 3.00A
- 8B3D EM 2.60A
- 8B3F EM 3.10A
- 9BZ0 EM 1.90A
- 9ER2 EM 3.30A
- 9FD2 EM 3.40A
- 9HWG EM 3.50A
A predicted model is available from AlphaFold.
Gene Ontology · 40
- GO:0016604 nuclear body
- GO:0005730 nucleolus
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0090734 site of DNA damage
- GO:0008023 transcription elongation factor complex
- GO:0005524 ATP binding
- GO:0016887 ATP hydrolysis activity
- GO:0008094 ATP-dependent activity, acting on DNA
- GO:0140658 ATP-dependent chromatin remodeler activity
- GO:0140664 ATP-dependent DNA damage sensor activity
- GO:0003682 chromatin binding
- GO:0140463 chromatin-protein adaptor activity
- GO:0003677 DNA binding
- GO:0004386 helicase activity
- GO:0030296 protein tyrosine kinase activator activity
- GO:0070063 RNA polymerase binding
- GO:0006284 base-excision repair
- GO:0006338 chromatin remodeling
- GO:0000077 DNA damage checkpoint signaling
- GO:0042262 DNA protection
- GO:0006281 DNA repair
- GO:0097680 double-strand break repair via classical nonhomologous end joining
- GO:2001033 negative regulation of double-strand break repair via nonhomologous end joining
- GO:0022008 neurogenesis
- GO:0030182 neuron differentiation
- GO:0031175 neuron projection development
- GO:0045739 positive regulation of DNA repair
- GO:0032786 positive regulation of DNA-templated transcription, elongation
- GO:1905168 positive regulation of double-strand break repair via homologous recombination
- GO:0045943 positive regulation of transcription by RNA polymerase I
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0045945 positive regulation of transcription by RNA polymerase III
- GO:0071168 protein localization to chromatin
- GO:0032784 regulation of DNA-templated transcription elongation
- GO:0034243 regulation of transcription elongation by RNA polymerase II
- GO:0006979 response to oxidative stress
- GO:0000012 single strand break repair
- GO:0006366 transcription by RNA polymerase II
- GO:0006283 transcription-coupled nucleotide-excision repair
Disease associations
- Cockayne syndrome type 2 MONDO:0019570
- cerebrooculofacioskeletal syndrome 1 MONDO:0008955
- de Sanctis-Cacchione syndrome MONDO:0010217
- UV-sensitive syndrome 1 MONDO:0010909
- age related macular degeneration 5 MONDO:0013409
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- DNA excision repair protein ERCC-6 0.96
- Probable ATP-dependent DNA helicase CHR12 0.81
- SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 homolog 0.80
- Lymphoid-specific helicase 0.79
- Probable chromatin-remodeling complex ATPase chain 0.79
- DNA excision repair protein ERCC-6-like 0.79
- ATP-dependent chromatin remodeler CHD6 0.79
- ATP-dependent chromatin remodeler CHD6 0.79
- SWI/SNF chromatin remodeling complex core catalytic subunit swsn-4 0.79
- ATP-dependent chromatin remodeler CHD6 0.78
- Lymphoid-specific helicase 0.78
- Lymphocyte-specific helicase 0.78
Co-cited proteins · studied together in the literature
- DNA excision repair protein ERCC-8 13 shared papers
- UV-stimulated scaffold protein A 9 shared papers
- Chimeric ERCC6-PGBD3 protein 2 shared papers
- PiggyBac transposable element-derived protein 3 2 shared papers
- DNA excision repair protein ERCC-5 2 shared papers
- Elongin-A 1 shared papers
- SWI/SNF complex subunit SMARCC2 1 shared papers
- E3 ubiquitin-protein ligase RBX1 4 shared papers
- Transcription elongation factor 1 homolog 1 shared papers
- DNA repair protein complementing XP-A cells homolog 1 shared papers
- Telomere-associated protein RIF1 1 shared papers
- Ubiquitin C-terminal hydrolase 7 3 shared papers
Literature · 49 cited papers
- Transcription-coupled DNA-protein crosslink repair by CSB and CRL4CSA-mediated degradation. Nat. Cell Biol. · 2024
- Transcription-coupled repair of DNA-protein cross-links depends on CSA and CSB. Nat. Cell Biol. · 2024
- Structural basis for RNA polymerase II ubiquitylation and inactivation in transcription-coupled repair. Nat. Struct. Mol. Biol. · 2024
- PMID 34919821 Mol. Cell · 2021
- Structural basis of human transcription-DNA repair coupling. Nature · 2021
- The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II. Nat. Commun. · 2020
- Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair. Cell · 2020
- CSA and CSB play a role in the response to DNA breaks. Oncotarget · 2018
- ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair pathway choice. Nat. Commun. · 2017
- Cockayne syndrome B protein regulates recruitment of the Elongin A ubiquitin ligase to sites of DNA damage. J. Biol. Chem. · 2017
- Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
- The C-terminal Region and SUMOylation of Cockayne Syndrome Group B Protein Play Critical Roles in Transcription-coupled Nucleotide Excision Repair. J. Biol. Chem. · 2016
- … and 37 more in the literature graph