title: ELL, a novel TFIIH partner, is involved in transcription restart after DNA repair.
abstract: DNA lesions that block transcription may cause cell death even when repaired, if transcription does not restart to reestablish cellular metabolism. However, transcription resumption after individual DNA-lesion repair remains poorly described in mechanistic terms and its players are largely unknown. The general transcription factor II H (TFIIH) is a major actor of both nucleotide excision repair subpathways of which transcription-coupled repair highlights the interplay between DNA repair and transcription. Using an unbiased proteomic approach, we have identified the protein eleven-nineteen lysine-rich leukemia (ELL) as a TFIIH partner. Here we show that ELL is recruited to UV-damaged chromatin in a Cdk7- dependent manner (a component of the cyclin-dependent activating kinase subcomplex of TFIIH). We demonstrate that depletion of ELL strongly hinders RNA polymerase II (RNA Pol II) transcription resumption after lesion removal and DNA gap filling. Lack of ELL was also observed to increase RNA Pol II retention to the chromatin during this process. Identifying ELL as an essential player for RNA Pol II restart during cellular DNA damage response opens the way to obtaining a mechanistic description of transcription resumption after DNA repair.
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, F-31077 Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Mourgues
authors.forename: Violette
authors.initials: V
authors.lastname: Gautier
authors.forename: Anna
authors.initials: A
authors.lastname: Lagarou
authors.forename: Christine
authors.initials: C
authors.lastname: Bordier
authors.forename: Amandine
authors.initials: A
authors.lastname: Mourcet
authors.forename: Joris
authors.initials: J
authors.lastname: Slingerland
authors.forename: Lara
authors.initials: L
authors.lastname: Kaddoum
authors.forename: Frédéric
authors.initials: F
authors.lastname: Coin
authors.forename: Wim
authors.initials: W
authors.lastname: Vermeulen
authors.forename: Anne
authors.initials: A
authors.lastname: Gonzales de Peredo
authors.forename: Bernard
authors.initials: B
authors.lastname: Monsarrat
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Mari
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Giglia-Mari
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000502:physiology*; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D051758:Transcription Factor TFIIH / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D035602:Transcriptional Elongation Factors / Q000378:metabolism*
chemical_list: D017931:DNA Primers; C090862:ELL protein, human; D035602:Transcriptional Elongation Factors; D051758:Transcription Factor TFIIH; D012319:RNA Polymerase II
keywords: CAK; Cockayne syndrome; LEC; TCR; elongation factor