Summary
Basic Information
Immunogen
AA 242-261 of human ERCC6
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.
Formulations & Storage [For reference only, actual COA shall prevail!]
Buffer
0.1M Tris HCl, pH 7.5
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.
Target
Full Name
ERCC Excision Repair 6, Chromatin Remodeling Factor
Introduction
This gene encodes a DNA-binding protein that is important in transcription-coupled excision repair. The encoded protein has ATP-stimulated ATPase activity, interacts with several transcription and excision repair proteins, and may promote complex formation at DNA repair sites. Mutations in this gene are associated with Cockayne syndrome type B and cerebrooculofacioskeletal syndrome 1. Alternative splicing occurs between a splice site from exon 5 of this gene to the 3' splice site upstream of the open reading frame (ORF) of the adjacent gene, piggyback-derived-3 (GeneID:267004), which activates the alternative polyadenylation site downstream of the piggyback-derived-3 ORF. The resulting transcripts encode a fusion protein that shares sequence with the product of each individual gene.
Alternative Names
ERCC Excision Repair 6, Chromatin Remodeling Factor; Excision Repair Cross-Complementing Rodent Repair Deficiency, Complementation Group 6; Excision Repair Cross-Complementation Group 6; Cockayne Syndrome Protein CSB; ATP-Dependent Helicase ERCC6; CSB; DNA Excision Repair Protein ERCC-6; Cockayne Syndrome Group B Protein; Chimeric ERCC6-PGBD3 Protein; Cockayne Syndrome B Protein; Chimeric CSB-PGBD3 Protein; ERCC6-PGBD3 Fusion Protein
Research Area
Essential factor involved in transcription-coupled nucleotide excision repair which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes (PubMed:20541997, PubMed:26620705, PubMed:16246722).
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 (PubMed:15548521).
It is required for transcription-coupled repair complex formation (PubMed:16916636).
It recruits the CSA complex (DCX(ERCC8) complex), nucleotide excision repair proteins and EP300 to the sites of RNA polymerase II-blocking lesions (PubMed:16916636).
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 (PubMed:25820262).
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 (PubMed:25820262).
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 (PubMed:25820262).
Acts as a chromatin remodeler at DSBs; DNA-dependent ATPase-dependent activity is essential for this function. Remodels chromatin by evicting histones from chromatin flanking DSBs, limiting RIF1 accumulation at DSBs thereby promoting BRCA1-mediated HR (PubMed:29203878).
Required for stable recruitment of ELOA and CUL5 to DNA damage sites (PubMed:28292928).
Involved in UV-induced translocation of ERCC8 to the nuclear matrix (PubMed:26620705).
Essential for neuronal differentiation and neuritogenesis; regulates transcription and chromatin remodeling activities required during neurogenesis (PubMed:24874740).
Biological Process
ATP-dependent chromatin remodeling Source: UniProtKB
Base-excision repair Source: UniProtKB
DNA damage checkpoint signaling Source: UniProtKB
DNA duplex unwinding Source: GOC
DNA repair Source: UniProtKB
Double-strand break repair via classical nonhomologous end joining Source: UniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
JNK cascade Source: Ensembl
Multicellular organism growth Source: Ensembl
Negative regulation of double-strand break repair via nonhomologous end joining Source: UniProtKB
Neurogenesis Source: UniProtKB
Neuron differentiation Source: UniProtKB
Neuron projection development Source: UniProtKB
Photoreceptor cell maintenance Source: Ensembl
Positive regulation of DNA repair Source: UniProtKB
Positive regulation of DNA-templated transcription, elongation Source: UniProtKB
Positive regulation of double-strand break repair via homologous recombination Source: UniProtKB
Positive regulation of transcription initiation from RNA polymerase II promoter Source: Ensembl
Pyrimidine dimer repair Source: Ensembl
Regulation of DNA-templated transcription, elongation Source: UniProtKB
Response to gamma radiation Source: Ensembl
Response to oxidative stress Source: UniProtKB
Response to superoxide Source: Ensembl
Response to toxic substance Source: Ensembl
Response to UV Source: UniProtKB
Response to UV-B Source: Ensembl
Response to X-ray Source: Ensembl
Single strand break repair Source: UniProtKB
Transcription by RNA polymerase II Source: UniProtKB
Transcription-coupled nucleotide-excision repair Source: UniProtKB
Transcription elongation from RNA polymerase I promoter Source: Ensembl
Involvement in disease
Cockayne syndrome B (CSB):
A rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer.
Cerebro-oculo-facio-skeletal syndrome 1 (COFS1):
A disorder of prenatal onset characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. COFS is considered to be part of the nucleotide-excision repair disorders spectrum that include also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome.
De Sanctis-Cacchione syndrome (DSC):
An autosomal recessive syndrome consisting of xeroderma pigmentosum associated with severe neurological and developmental involvement. In addition to the clinical signs of xeroderma pigmentosum, patients present with mental retardation, dwarfism, gonadal hypoplasia, microcephaly and various neurologic complications of early onset.
Macular degeneration, age-related, 5 (ARMD5):
A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
UV-sensitive syndrome 1 (UVSS1):
An autosomal recessive disorder characterized by cutaneous photosensitivity and mild freckling in the absence of neurological abnormalities or skin tumors.
PTM
Phosphorylated in a cell cycle-dependent manner at Ser-158 by cyclin A-CDK2 and at Ser-10 by ATM in response to DNA damage (PubMed:29203878). Phosphorylation at these two sites promotes the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain, thereby probably releasing the inhibitory effect of the N-terminal domain on its ATPase activity (PubMed:29203878). Phosphorylation is essential for its chromatin remodeling activity (PubMed:29203878).
Ubiquitinated at the C-terminus. Ubiquitination by the CSA complex leads to ERCC6 proteasomal degradation in a UV-dependent manner. Stabilized following interaction with KIAA1530/UVSSA, which promotes recruitment of deubiquitinating enzyme USP7, leading to deubiquitination of ERCC6 thereby preventing UV-induced degradation of ERCC6 by the proteasome.
Sumoylation at Lys-205 in an UV-radiation-dependent manner is essential for its transcription-coupled nucleotide excision repair activity.
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Datasheet