Target intelligence / Profile preview

General transcription and DNA repair factor IIH helicase subunit XPB (XPB)

Target
XPB
Molecular classification
DNA helicase, Transcription factor subunit, DNA repair protein, Enzyme (EC 5.6.2.4, 3.6.1)
01

Overview

General transcription and DNA repair factor IIH helicase subunit XPB (XPB/ERCC3) is an ATP-dependent DNA helicase that is a critical part of the TFIIH complex, which has dual roles in the initiation of RNA polymerase II-dependent gene transcription and in nucleotide excision DNA repair. XPB unwinds DNA with 3'-5' polarity to facilitate repair and transcription, acting as a wedge to open DNA strands at sites of damage and at promoters for gene activation[1][2][3][4]. Mutations in XPB/ERCC3 are associated with several genetic syndromes characterized by photosensitivity, abnormal development, and markedly increased cancer risk, reflecting its essential function in genome maintenance; small molecules such as triptolide may selectively inhibit XPB for potential cancer therapy, but this raises substantial safety and selectivity concerns because of XPB’s central role in cellular homeostasis[1][2][3].

Other names
ERCC3TFIIH 89 kDa subunitTFIIH p89BTF2RAD25Ssl2DNA excision repair protein ERCC-3DNA 3'-5' helicase/translocase XPBXeroderma pigmentosum group B-complementing proteinTFIIH subunit XPB[2][3]
02

Mechanism of action

Inhibition of TFIIH complex activity, preventing promoter opening and transcription initiation (triptolide); Blocking DNA unwinding and hence hindering DNA repair and gene transcription

03

Biological functions

Transcription initiation (RNA polymerase II-dependent)Nucleotide excision repairTranscription-coupled DNA repairDNA unwinding (3'-5' direction)Chromatin opening
04

Disease associations

Xeroderma pigmentosum (XP, group B)Cockayne syndromeTrichothiodystrophyXP/CS complex (XP with Cockayne syndrome features)Cancer (high cancer risk with loss of DNA repair function)Photosensitivity disordersOther DNA repair disorders
05

Safety considerations

Risk of impaired DNA repair leading to mutagenesis and cancerPotential for adverse effects on normal transcription and cell viability if inhibitedGlobal impact on cell proliferation and tissue integrity
06

Interacting drugs

Triptolide
07

Biomarkers

ERCC3/XPB mutation status for risk of XP, Cockayne syndrome, trichothiodystrophyPhotosensitivity and DNA repair deficiency phenotypes

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