XPB (

xeroderma pigmentosum Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in su ...

type B) is an ATP-dependent

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

helicase Helicases are a class of enzymes that are vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic double helix, separating the two hybridized ...

in humans that is a part of the TFIIH

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

complex.

Structure

The 3D-structure of the archaeal homolog of XPB has been solved by X-ray crystallography by Dr. John Tainer and his group at

The Scripps Research Institute Scripps Research is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California, the institute has over 170 laboratories employing 2,100 scientists, tec ...

Function

XPB plays a significant role in normal basal transcription, transcription coupled repair (TCR), and

nucleotide excision repair Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. Intercalation (biochemistry), intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single ...

(NER). Purified XPB has been shown to unwind DNA with 3’-5’ polarity. The function of the XPB(ERCC3) protein in NER is to assist in unwinding the

double helix after damage is initially recognized. NER is a multi-step pathway that removes a wide range of different DNA damages that distort normal base pairing. Such damages include bulky chemical adducts, UV-induced pyrimidine dimers, and several forms of

oxidative damage Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal r ...

. Mutations in the XPB(ERCC3) gene can lead, in humans, to

(XP) or XP combined with

Cockayne syndrome Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight ( photo ...

(XPCS). Mutant XPB cells from individuals with the XPCS phenotype are sensitive to UV irradiation and acute oxidative stress. XPB helicase is also a component of the

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

-mediated programmed cell death (

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

) pathway.

Disorders

Mutations in XPB and other related complementation groups, XPA-XPG, leads to a number of genetic disorders such as

Xeroderma pigmentosum Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in su ...

Cockayne's syndrome Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight (photose ...

, and

trichothiodystrophy Trichothiodystrophy (TTD) is an autosomal recessive inherited disorder characterised by brittle hair and intellectual impairment. The word breaks down into ''tricho'' – "hair", '' thio'' – "sulphur", and ''dystrophy'' – "wasting away" or lit ...

Interactions

XPB has been shown to interact with: * BCR gene, * CDK7, * ERCC2, * GTF2H1, * GTF2H2, * GTF2H4, * GTF2H5, *

P53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

, * PSMC5, and * XPC.

Small molecule inhibitors

Potent, bioactive natural products like triptolide that inhibit mammalian transcription via inhibition of the XPB subunit of the general transcription factor TFIIH has been recently reported as a glucose conjugate for targeting hypoxic cancer cells with increased glucose transporter expression.

References

External links

GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum
* {{DEFAULTSORT:Xpb EC 3.6.4 DNA replication Helicases