Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions.
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.
Shimizu
Yuichiro
Y
Cellular Physiology Laboratory, RIKEN Discovery Research Institute, Wako, Saitama 351-0198, Japan.
Uchimura
Yasuhiro
Y
Dohmae
Naoshi
N
Saitoh
Hisato
H
Hanaoka
Fumio
F
Sugasawa
Kaoru
K
J Biol Chem. 2001 Jun 1;276(22):18665-72
11279143
J Biol Chem. 2000 Oct 27;275(43):33449-56
10938281
Mutat Res. 2000 Aug 30;460(3-4):165-81
10946227
Curr Biol. 2005 Apr 12;15(7):616-23
15823533
EMBO J. 1999 Jul 1;18(13):3834-44
10393198
Cancer Res. 1998 Oct 1;58(19):4402-9
9766670
Mol Cell. 1998 Aug;2(2):223-32
9734359
Bioessays. 2001 Mar;23(3):270-81
11223884
Annu Rev Biochem. 1999;68:255-85
10872450
Biochemistry. 2003 May 6;42(17):5003-12
12718543
Nucleic Acids Res. 2005 Jul 19;33(13):4023-34
16030353
J Biol Chem. 2002 Oct 18;277(42):39926-36
12161446
Genes Dev. 2000 Feb 1;14(3):349-59
10673506
Mol Cell Biol. 1996 Sep;16(9):4852-61
8756644
EMBO J. 2002 Mar 15;21(6):1456-64
11889051
DNA Repair (Amst). 2004 Oct 5;3(10):1285-95
15336624
Mol Cell. 2001 Jul;8(1):213-24
11511374
J Biol Chem. 2003 Oct 3;278(40):38586-92
12874288
EMBO J. 2003 Oct 1;22(19):5293-303
14517266
Cancer Res. 2000 Mar 15;60(6):1571-9
10749125
Science. 2007 May 25;316(5828):1160-6
17525332
J Biol Chem. 2001 Sep 7;276(36):33569-75
11438542
J Biol Chem. 2008 Nov 21;283(47):32680-90
18805789
DNA Repair (Amst). 2004 Apr 1;3(4):379-86
15010313
Mol Cell Biol. 1997 Dec;17(12):6915-23
9372923
Anal Biochem. 2004 Aug 1;331(1):204-6
15246018
EMBO J. 2003 Jan 2;22(1):164-73
12505994
J Biol Chem. 1995 Feb 10;270(6):2415-8
7852297
Cell. 2005 May 6;121(3):387-400
15882621
Mol Cell Biol. 2005 Jul;25(13):5664-74
15964821
Prog Nucleic Acid Res Mol Biol. 2001;68:365-86
11554311
EMBO J. 1999 Dec 1;18(23):6599-609
10581234
Mutat Res. 2001 Sep 1;480-481:277-84
11506820
Carcinogenesis. 1992 Mar;13(3):321-8
1547519
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3969-74
10097147
J Biol Chem. 2003 Mar 7;278(10):8739-44
12493755
J Biol Chem. 2001 Nov 9;276(45):41991-7
11526119
Oncogene. 2000 Oct 12;19(43):5034-7
11042691
EMBO J. 1994 Apr 15;13(8):1831-43
8168482
Biochemistry. 2004 Mar 16;43(10):2682-7
15005603
Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12130-5
15302935
Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15071-6
14614141
Curr Biol. 1999 Feb 25;9(4):174-85
10074426
DNA Repair (Amst). 2002 Jan 22;1(1):95-107
12509299
Nature. 2005 Jun 16;435(7044):979-82
15959518
J Biol Chem. 1998 Aug 7;273(32):20007-14
9685338
Mol Cell. 2000 Jun;5(6):1059-65
10912000
DNA Repair (Amst). 2007 Apr 1;6(4):489-504
17116428
J Invest Dermatol. 1995 Jan;104(1):68-73
7798643
Nature. 2007 Oct 4;449(7162):570-5
17882165
Mol Cell. 2003 Jun;11(6):1647-59
12820976
J Biol Chem. 1998 Aug 14;273(33):20728-36
9694815
Nature. 1996 Oct 24;383(6602):735-8
8878487
J Biol Chem. 1994 Sep 9;269(36):22749-57
8077226
EMBO J. 2001 Aug 1;20(15):4278-86
11483530
EMBO J. 2006 Sep 20;25(18):4305-15
16957781
Mol Cell. 2002 Feb;9(2):265-77
11864601
Chem Rev. 2006 Feb;106(2):253-76
16464005
J Biol Chem. 1999 Jan 1;274(1):67-74
9867812
Cell. 1998 Jan 9;92(1):117-29
9489705
Genes Dev. 2003 Jul 1;17(13):1630-45
12815074
Genes Dev. 2001 Mar 1;15(5):507-21
11238373