XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients

Shinsuke Ito; Isao Kuraoka; Pierre Chymkowitch; Emmanuel Compe; Arato Takedachi; Chie Ishigami; Frédéric Coin; Jean-Marc Egly; Kiyoji Tanaka

doi:10.1016/j.molcel.2007.03.013

XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients

Mol Cell. 2007 Apr 27;26(2):231-43. doi: 10.1016/j.molcel.2007.03.013.

Authors

Shinsuke Ito¹, Isao Kuraoka, Pierre Chymkowitch, Emmanuel Compe, Arato Takedachi, Chie Ishigami, Frédéric Coin, Jean-Marc Egly, Kiyoji Tanaka

Affiliation

¹ Laboratories for Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.

PMID: 17466625
DOI: 10.1016/j.molcel.2007.03.013

Abstract

Mutations in the human XPG gene give rise to an inherited photosensitive disorder, xeroderma pigmentosum (XP) associated with Cockayne syndrome (XP-G/CS). The clinical features of CS in XP-G/CS patients are difficult to explain on the basis of a defect in nucleotide excision repair (NER). We found that XPG forms a stable complex with TFIIH, which is active in transcription and NER. Mutations in XPG found in XP-G/CS patient cells that prevent the association with TFIIH also resulted in the dissociation of CAK and XPD from the core TFIIH. As a consequence, the phosphorylation and transactivation of nuclear receptors were disturbed in XP-G/CS as well as xpg(-/-) MEF cells and could be restored by expression of wild-type XPG. These results provide an insight into the role of XPG in the stabilization of TFIIH and the regulation of gene expression and provide an explanation of some of the clinical features of XP-G/CS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Cell Line
Cockayne Syndrome / complications
Cockayne Syndrome / genetics
Cockayne Syndrome / metabolism*
Cyclin-Dependent Kinase-Activating Kinase
Cyclin-Dependent Kinases / metabolism
DNA Damage
DNA Repair
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Drug Stability
Endonucleases / genetics
Endonucleases / metabolism*
HeLa Cells
Humans
In Vitro Techniques
Models, Biological
Mutation
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
RNA, Small Interfering / genetics
Receptors, Cytoplasmic and Nuclear / metabolism
Transcription Factor TFIIH / metabolism*
Transcription Factors / genetics
Transcription Factors / metabolism*
Transcriptional Activation
Xeroderma Pigmentosum / complications
Xeroderma Pigmentosum / genetics
Xeroderma Pigmentosum / metabolism*

Substances

DNA excision repair protein ERCC-5
DNA-Binding Proteins
Nuclear Proteins
RNA, Small Interfering
Receptors, Cytoplasmic and Nuclear
Transcription Factors
Transcription Factor TFIIH
Cyclin-Dependent Kinases
Endonucleases
Cyclin-Dependent Kinase-Activating Kinase