ERCC3

This gene encodes an ATP-dependent DNA helicase that functions in nucleotide excision repair. The encoded protein is a subunit of basal transcription factor 2 (TFIIH) and, therefore, also functions in class II transcription. Mutations in this gene are associated with Xeroderma pigmentosum B, Cockayne's syndrome, and trichothiodystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit

ATP-dependent 3'-5' DNA helicase, component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. The ATPase activity of XPB/ERCC3, but not its helicase activity, is required for DNA opening. In transcription, TFIIH has an essential role in transcription initiation (PubMed:8157004, PubMed:30894545).

When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape (PubMed:8157004).

The ATP-dependent helicase activity of XPB/ERCC3 is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.

Apoptotic process Source: UniProtKB
DNA repair Source: UniProtKB
DNA topological change Source: UniProtKB
Embryonic organ development Source: GO_Central
Hair cell differentiation Source: UniProtKB
Nucleotide-excision repair Source: UniProtKB
Nucleotide-excision repair, DNA duplex unwinding Source: UniProtKB
Nucleotide-excision repair, DNA incision Source: UniProtKB
Positive regulation of apoptotic process Source: UniProtKB
Protein localization Source: UniProtKB
Regulation of mitotic cell cycle phase transition Source: UniProtKB
Response to hypoxia Source: Ensembl
Response to oxidative stress Source: UniProtKB
Response to UV Source: UniProtKB
Transcription by RNA polymerase II Source: UniProtKB
Transcription-coupled nucleotide-excision repair Source: UniProtKB
Transcription elongation from RNA polymerase II promoter Source: Reactome
Transcription elongation from RNA polymerase I promoter Source: Ensembl
Transcription initiation from RNA polymerase II promoter Source: GO_Central
UV protection Source: Ensembl

Nucleus

Xeroderma pigmentosum complementation group B (XP-B):
An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. Some XP-B patients present features of Cockayne syndrome, including cachectic dwarfism, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. The phenotype combining xeroderma pigmentosum and Cockayne syndrome traits is referred to as XP-CS complex.
Trichothiodystrophy 2, photosensitive (TTD2):
A form of trichothiodystrophy, an autosomal recessive disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder.