title: ARCH domain of XPD, an anchoring platform for CAK that conditions TFIIH DNA repair and transcription activities.
abstract: The xeroderma pigmentosum group D (XPD) helicase is a subunit of transcription/DNA repair factor, transcription factor II H (TFIIH) that catalyzes the unwinding of a damaged DNA duplex during nucleotide excision repair. Apart from two canonical helicase domains, XPD is composed of a 4Fe-S cluster domain involved in DNA damage recognition and a module of uncharacterized function termed the "ARCH domain." By investigating the consequences of a mutation found in a patient with trichothiodystrophy, we show that the ARCH domain is critical for the recruitment of the cyclin-dependent kinase (CDK)-activating kinase (CAK) complex. Indeed, this mutation not only affects the interaction with the MAT1 CAK subunit, thereby decreasing the in vitro basal transcription activity of TFIIH itself and impeding the efficient recruitment of the transcription machinery on the promoter of an activated gene, but also impairs the DNA unwinding activity of XPD and the nucleotide excision repair activity of TFIIH. We further demonstrate the role of CAK in downregulating the XPD helicase activity within TFIIH. Taken together, our results identify the ARCH domain of XPD as a platform for the recruitment of CAK and as a potential molecular switch that might control TFIIH composition and play a key role in the conversion of TFIIH from a factor active in transcription to a factor involved in DNA repair.
authors: Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université de Strasbourg, Illkirch Cedex 67404, France.
authors: Wassim
authors: W
authors: Abdulrahman
authors: Izarn
authors: I
authors: Iltis
authors: Laura
authors: L
authors: Radu
authors: Cathy
authors: C
authors: Braun
authors: Anne
authors: A
authors: Maglott-Roth
authors: Christophe
authors: C
authors: Giraudon
authors: Jean-Marc
authors: JM
authors: Egly
authors: Arnaud
authors: A
authors: Poterszman
mesh_terms: D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004260:DNA Repair; D000070819:Discoidin Domain Receptor 1; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051758:Transcription Factor TFIIH / Q000502:physiology*; D014158:Transcription, Genetic; D054463:Trichothiodystrophy Syndromes / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D007506:Iron-Sulfur Proteins; D051758:Transcription Factor TFIIH; C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
references: EMBO J. 2012 Jan 18;31(2):494-502
references: 22081108
references: Mol Cell. 2010 Aug 27;39(4):632-40
references: 20797633
references: Anal Biochem. 2009 Feb 15;385(2):383-5
references: 19061853
references: J Exp Med. 2009 Dec 21;206(13):3031-46
references: 19934020
references: Mol Cell. 2003 Jun;11(6):1635-46
references: 12820975
references: Nature. 1994 Jan 6;367(6458):91-4
references: 8107780
references: Nat Struct Mol Biol. 2004 Jul;11(7):616-22
references: 15195146
references: Anal Biochem. 2010 Dec 1;407(1):34-43
references: 20624369
references: Curr Opin Struct Biol. 2010 Jun;20(3):313-24
references: 20456941
references: EMBO J. 1988 Oct;7(10):3263-9
references: 2846277
references: Genes Dev. 2000 Feb 1;14(3):349-59
references: 10673506
references: Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):1949-54
references: 22308316
references: PLoS Biol. 2008 Jun 24;6(6):e149
references: 18578568
references: Cell. 2000 Sep 1;102(5):609-13
references: 11007479
references: Nat Genet. 1998 Oct;20(2):184-8
references: 9771713
references: Hum Mol Genet. 2002 Nov 1;11(23):2919-28
references: 12393803
references: Carcinogenesis. 2000 Mar;21(3):453-60
references: 10688865
references: Cell. 1997 Jul 11;90(1):97-107
references: 9230306
references: EMBO J. 2011 Feb 2;30(3):468-79
references: 21157430
references: Nature. 1995 Oct 12;377(6549):557-60
references: 7566158
references: DNA Repair (Amst). 2010 Jan 2;9(1):2-10
references: 19931493
references: Nat Methods. 2006 Dec;3(12):1021-32
references: 17117155
references: PLoS Genet. 2010 Mar 12;6(3):e1000876
references: 20300654
references: J Am Chem Soc. 2011 Oct 19;133(41):16378-81
references: 21939244
references: Nature. 2003 Jul 10;424(6945):228-32
references: 12853965
references: J Biol Chem. 1997 Nov 7;272(45):28175-8
references: 9353262
references: Mol Cell. 2004 Oct 22;16(2):187-97
references: 15494306
references: Nucleic Acids Res. 2011 Jul;39(12):5025-35
references: 21385826
references: Cell. 2008 May 30;133(5):801-12
references: 18510925
references: J Biol Chem. 2000 Jul 28;275(30):22815-23
references: 10801852
references: DNA Repair (Amst). 2011 Jul 15;10(7):714-21
references: 21592869
references: J Biol Chem. 1991 Nov 5;266(31):20940-5
references: 1939143
references: Cancer Res. 1995 Dec 1;55(23):5656-63
references: 7585650
references: Nature. 1992 Aug 20;358(6388):641-5
references: 1495560
references: Mol Cell. 2010 Apr 9;38(1):54-66
references: 20385089
references: Mol Cell. 1999 Jan;3(1):87-95
references: 10024882
references: Am J Hum Genet. 1998 Oct;63(4):1036-48
references: 9758621
references: Arch Dermatol. 1980 Dec;116(12):1375-84
references: 7458366
references: Mol Cell Biol. 2009 Jan;29(2):315-23
references: 18981214
references: Mol Cell. 2008 Jul 11;31(1):9-20
references: 18614043
references: Cell. 2000 Sep 1;102(5):599-607
references: 11007478
references: Nat Struct Mol Biol. 2005 Jul;12(7):603-7
references: 15937491
references: Nat Genet. 2004 Jul;36(7):714-9
references: 15220921
references: Mol Cell. 2007 Apr 27;26(2):245-56
references: 17466626
references: Mol Cell. 2009 May 15;34(3):387-93
references: 19450536
references: Nat Rev Mol Cell Biol. 2012 May 10;13(6):343-54
references: 22572993
references: J Cell Sci. 2006 Sep 15;119(Pt 18):3866-75
references: 16940351
references: Cell. 2008 May 30;133(5):789-800
references: 18510924
references: Mol Cell Biol. 2009 Oct;29(20):5455-64
references: 19667075
references: DNA Repair (Amst). 2011 Jul 15;10(7):697-713
references: 21571596
references: Nat Struct Mol Biol. 2008 Sep;15(9):980-4
references: 19172752
references: Genes Dev. 2001 Jan 1;15(1):15-23
references: 11156600
references: Mol Cell. 2000 Jul;6(1):127-37
references: 10949034
references: J Biol Chem. 2001 Sep 21;276(38):35328-33
references: 11445587
references: Cell. 2002 Apr 5;109(1):125-35
references: 11955452
references: Mol Cell Biol. 2005 Jul;25(14):6065-76
references: 15988019
references: Mol Cell. 2007 Apr 27;26(2):231-43
references: 17466625