title: Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions.
abstract: We showed that XPC complex, which is a DNA damage detector for nucleotide excision repair, stimulates activity of thymine DNA glycosylase (TDG) that initiates base excision repair. XPC appeared to facilitate the enzymatic turnover of TDG by promoting displacement from its own product abasic site, although the precise mechanism underlying this stimulation has not been clarified. Here we show that XPC has only marginal effects on the activity of E. coli TDG homolog (EcMUG), which remains bound to the abasic site like human TDG but does not significantly interacts with XPC. On the contrary, XPC significantly stimulates the activities of sumoylated TDG and SMUG1, both of which exhibit quite different enzymatic kinetics from unmodified TDG but interact with XPC. These results point to importance of physical interactions for stimulation of DNA glycosylases by XPC and have implications in the molecular mechanisms underlying mutagenesis and carcinogenesis in XP-C patients.
authors.affiliation: Cellular Physiology Laboratory, RIKEN Discovery Research Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Uchimura
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.forename: Hisato
authors.initials: H
authors.lastname: Saitoh
authors.forename: Fumio
authors.initials: F
authors.lastname: Hanaoka
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugasawa
references.citation: J Biol Chem. 2001 Jun 1;276(22):18665-72
references.pmid: 11279143
references.citation: J Biol Chem. 2000 Oct 27;275(43):33449-56
references.pmid: 10938281
references.citation: Mutat Res. 2000 Aug 30;460(3-4):165-81
references.pmid: 10946227
references.citation: Curr Biol. 2005 Apr 12;15(7):616-23
references.pmid: 15823533
references.citation: EMBO J. 1999 Jul 1;18(13):3834-44
references.pmid: 10393198
references.citation: Cancer Res. 1998 Oct 1;58(19):4402-9
references.pmid: 9766670
references.citation: Mol Cell. 1998 Aug;2(2):223-32
references.pmid: 9734359
references.citation: Bioessays. 2001 Mar;23(3):270-81
references.pmid: 11223884
references.citation: Annu Rev Biochem. 1999;68:255-85
references.pmid: 10872450
references.citation: Biochemistry. 2003 May 6;42(17):5003-12
references.pmid: 12718543
references.citation: Nucleic Acids Res. 2005 Jul 19;33(13):4023-34
references.pmid: 16030353
references.citation: J Biol Chem. 2002 Oct 18;277(42):39926-36
references.pmid: 12161446
references.citation: Genes Dev. 2000 Feb 1;14(3):349-59
references.pmid: 10673506
references.citation: Mol Cell Biol. 1996 Sep;16(9):4852-61
references.pmid: 8756644
references.citation: EMBO J. 2002 Mar 15;21(6):1456-64
references.pmid: 11889051
references.citation: DNA Repair (Amst). 2004 Oct 5;3(10):1285-95
references.pmid: 15336624
references.citation: Mol Cell. 2001 Jul;8(1):213-24
references.pmid: 11511374
references.citation: J Biol Chem. 2003 Oct 3;278(40):38586-92
references.pmid: 12874288
references.citation: EMBO J. 2003 Oct 1;22(19):5293-303
references.pmid: 14517266
references.citation: Cancer Res. 2000 Mar 15;60(6):1571-9
references.pmid: 10749125
references.citation: Science. 2007 May 25;316(5828):1160-6
references.pmid: 17525332
references.citation: J Biol Chem. 2001 Sep 7;276(36):33569-75
references.pmid: 11438542
references.citation: J Biol Chem. 2008 Nov 21;283(47):32680-90
references.pmid: 18805789
references.citation: DNA Repair (Amst). 2004 Apr 1;3(4):379-86
references.pmid: 15010313
references.citation: Mol Cell Biol. 1997 Dec;17(12):6915-23
references.pmid: 9372923
references.citation: Anal Biochem. 2004 Aug 1;331(1):204-6
references.pmid: 15246018
references.citation: EMBO J. 2003 Jan 2;22(1):164-73
references.pmid: 12505994
references.citation: J Biol Chem. 1995 Feb 10;270(6):2415-8
references.pmid: 7852297
references.citation: Cell. 2005 May 6;121(3):387-400
references.pmid: 15882621
references.citation: Mol Cell Biol. 2005 Jul;25(13):5664-74
references.pmid: 15964821
references.citation: Prog Nucleic Acid Res Mol Biol. 2001;68:365-86
references.pmid: 11554311
references.citation: EMBO J. 1999 Dec 1;18(23):6599-609
references.pmid: 10581234
references.citation: Mutat Res. 2001 Sep 1;480-481:277-84
references.pmid: 11506820
references.citation: Carcinogenesis. 1992 Mar;13(3):321-8
references.pmid: 1547519
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3969-74
references.pmid: 10097147
references.citation: J Biol Chem. 2003 Mar 7;278(10):8739-44
references.pmid: 12493755
references.citation: J Biol Chem. 2001 Nov 9;276(45):41991-7
references.pmid: 11526119
references.citation: Oncogene. 2000 Oct 12;19(43):5034-7
references.pmid: 11042691
references.citation: EMBO J. 1994 Apr 15;13(8):1831-43
references.pmid: 8168482
references.citation: Biochemistry. 2004 Mar 16;43(10):2682-7
references.pmid: 15005603
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12130-5
references.pmid: 15302935
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15071-6
references.pmid: 14614141
references.citation: Curr Biol. 1999 Feb 25;9(4):174-85
references.pmid: 10074426
references.citation: DNA Repair (Amst). 2002 Jan 22;1(1):95-107
references.pmid: 12509299
references.citation: Nature. 2005 Jun 16;435(7044):979-82
references.pmid: 15959518
references.citation: J Biol Chem. 1998 Aug 7;273(32):20007-14
references.pmid: 9685338
references.citation: Mol Cell. 2000 Jun;5(6):1059-65
references.pmid: 10912000
references.citation: DNA Repair (Amst). 2007 Apr 1;6(4):489-504
references.pmid: 17116428
references.citation: J Invest Dermatol. 1995 Jan;104(1):68-73
references.pmid: 7798643
references.citation: Nature. 2007 Oct 4;449(7162):570-5
references.pmid: 17882165
references.citation: Mol Cell. 2003 Jun;11(6):1647-59
references.pmid: 12820976
references.citation: J Biol Chem. 1998 Aug 14;273(33):20728-36
references.pmid: 9694815
references.citation: Nature. 1996 Oct 24;383(6602):735-8
references.pmid: 8878487
references.citation: J Biol Chem. 1994 Sep 9;269(36):22749-57
references.pmid: 8077226
references.citation: EMBO J. 2001 Aug 1;20(15):4278-86
references.pmid: 11483530
references.citation: EMBO J. 2006 Sep 20;25(18):4305-15
references.pmid: 16957781
references.citation: Mol Cell. 2002 Feb;9(2):265-77
references.pmid: 11864601
references.citation: Chem Rev. 2006 Feb;106(2):253-76
references.pmid: 16464005
references.citation: J Biol Chem. 1999 Jan 1;274(1):67-74
references.pmid: 9867812
references.citation: Cell. 1998 Jan 9;92(1):117-29
references.pmid: 9489705
references.citation: Genes Dev. 2003 Jul 1;17(13):1630-45
references.pmid: 12815074
references.citation: Genes Dev. 2001 Mar 1;15(5):507-21
references.pmid: 11238373