Article
- The EMBO Journal (2004) 23, 4835 - 4846
- doi:10.1038/sj.emboj.7600480
Published online: 18 November 2004
Subject Categories:
Phosphorylation of XPB helicase regulates TFIIH nucleotide excision repair activity
Frédéric Coin1, Jérome Auriol1, Angel Tapias1, Pascale Clivio2, Wim Vermeulen3 and Jean-Marc Egly1
- Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, CU Strasbourg, France
- Institut de Chimie des Substances Naturelles du CNRS, ICSN-CNRS, Gif sur Yvette, France
- Department of Genetics, Medical Genetic Cluster, Erasmus MC, Rotterdam, The Netherlands
Correspondence to:
Jean-Marc Egly, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, CU de Strasbourg, France. Tel.: +33 388 65 34 47; Fax: +33 388 65 32 01; E-mail: egly@igbmc.u-strasbg.fr
Received 20 September 2004; Accepted 20 October 2004
Abstract
Nucleotide excision repair (NER) removes damage from DNA in a tightly regulated multiprotein process. The xeroderma pigmentosum group B (XPB) helicase subunit of TFIIH functions in NER and transcription. The serine 751 (S751) residue of XPB was found to be phosphorylated in vivo. This phosphorylation inhibits NER and the microinjection of a phosphomimicking XPB-S751E mutant is unable to correct the NER defect of XP-B cells. Conversely, XPB-S751 dephosphorylation or its substitution with alanine (S751A) restores NER both in vivo and in vitro. Surprisingly, phospho/dephosphorylation of S751 spares TFIIH-dependent transcription. Finally, the phosphorylation of XPB-S751 does not impair the TFIIH unwinding of the DNA around the lesion, but rather prevents the 5' incision triggered by the ERCC1-XPF endonuclease. These data support an additional role for XPB in promoting the incision of the damaged fragment and reveal a point of NER regulation on TFIIH without interference in its transcription activity.
Keywords:
- DNA damage response,
- GG-NER,
- helicase,
- phosphorylation,
- TFIIH
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