title: Molecular insights into the recruitment of TFIIH to sites of DNA damage.
abstract: XPB and XPD subunits of TFIIH are central genome caretakers involved in nucleotide excision repair (NER), although their respective role within this DNA repair pathway remains difficult to delineate. To obtain insight into the function of XPB and XPD, we studied cell lines expressing XPB or XPD ATPase-deficient complexes. We show the involvement of XPB, but not XPD, in the accumulation of TFIIH to sites of DNA damage. Recruitment of TFIIH occurs independently of the helicase activity of XPB, but requires two recently identified motifs, a R-E-D residue loop and a Thumb-like domain. Furthermore, we show that these motifs are specifically involved in the DNA-induced stimulation of the ATPase activity of XPB. Together, our data demonstrate that the recruitment of TFIIH to sites of damage is an active process, under the control of the ATPase motifs of XPB and suggest that this subunit functions as an ATP-driven hook to stabilize the binding of the TFIIH to damaged DNA.
authors.affiliation: Department of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch Graffenstaden, France.
authors.forename: Valentyn
authors.initials: V
authors.lastname: Oksenych
authors.forename: Bruno
authors.initials: B
authors.lastname: Bernardes de Jesus
authors.forename: Alexander
authors.initials: A
authors.lastname: Zhovmer
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Egly
authors.forename: Frédéric
authors.initials: F
authors.lastname: Coin
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D016415:Sequence Alignment; D051758:Transcription Factor TFIIH / Q000737:chemistry / Q000378:metabolism*
chemical_list: D051758:Transcription Factor TFIIH; D000251:Adenosine Triphosphatases; D004265:DNA Helicases