Flipping of alkylated DNA damage bridges base and nucleotide excision repair

被引：106

作者：

Tubbs, Julie L. ^{[1
,2
]}

Latypov, Vitaly ^{[3
]}

Kanugula, Sreenivas ^{[4
]}

Butt, Amna ^{[3
]}

Melikishvili, Manana ^{[5
]}

Kraehenbuehl, Rolf ^{[6
]}

Fleck, Oliver ^{[6
]}

Marriott, Andrew ^{[3
]}

Watson, Amanda J. ^{[3
]}

Verbeek, Barbara ^{[3
]}

McGown, Gail ^{[3
]}

Thorncroft, Mary ^{[3
]}

Santibanez-Koref, Mauro F. ^{[7
]}

Millington, Christopher ^{[8
]}

Arvai, Andrew S. ^{[1
,2
]}

Kroeger, Matthew D. ^{[1
,2
]}

Peterson, Lisa A. ^{[9
,10
]}

Williams, David M. ^{[8
]}

Fried, Michael G. ^{[5
]}

Margison, Geoffrey P. ^{[3
]}

Pegg, Anthony E. ^{[4
]}

Tainer, John A. ^{[1
,2
,11
]}

机构：

[1] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

[3] Univ Manchester, Paterson Inst Canc Res, Canc Res UK Carcinogenesis Grp, Manchester M20 4BX, Lancs, England

[4] Penn State Univ, Coll Med, Milton S Hershey Med Ctr, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA

[5] Univ Kentucky, Dept Mol & Cellular Biochem, Struct Biol Ctr, Lexington, KY 40536 USA

[6] Bangor Univ, NWCRF Inst, Bangor LL57 2UW, Gwynedd, Wales

[7] Univ Newcastle, Inst Human Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[8] Univ Sheffield, Dept Chem, Ctr Chem Biol, Sheffield S3 7HF, S Yorkshire, England

[9] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA

[10] Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN 55455 USA

[11] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA

来源：

NATURE | 2009年 / 459卷 / 7248期

关键词：

O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ESCHERICHIA-COLI; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; STRUCTURAL BASIS; ENDONUCLEASE-V; PROTEIN; RECOGNITION; BINDING; GENOME; SUBSTRATE;

D O I：

10.1038/nature08076

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Alkyltransferase-like proteins (ATLs) share functional motifs with the cancer chemotherapy target O-6-alkylguanine-DNA alkyltransferase (AGT) and paradoxically protect cells from the biological effects of DNA alkylation damage, despite lacking the reactive cysteine and alkyltransferase activity of AGT. Here we determine Schizosaccharomyces pombe ATL structures without and with damaged DNA containing the endogenous lesion O-6-methylguanine or cigarette-smoke-derived O-6-4-(3-pyridyl)-4-oxobutylguanine. These results reveal non-enzymatic DNA nucleotide flipping plus increased DNA distortion and binding pocket size compared to AGT. Our analysis of lesion-binding site conservation identifies new ATLs in sea anemone and ancestral archaea, indicating that ATL interactions are ancestral to present-day repair pathways in all domains of life. Genetic connections to mammalian XPG (also known as ERCC5) and ERCC1 in S. pombe homologues Rad13 and Swi10 and biochemical interactions with Escherichia coli UvrA and UvrC combined with structural results reveal that ATLs sculpt alkylated DNA to create a genetic and structural intersection of base damage processing with nucleotide excision repair.

引用

页码：808 / 813

页数：6

共 50 条

[1] DNA repair excision nuclease attacks undamaged DNA - A potential source of spontaneous mutations [J].

Branum, ME ;

Reardon, JT ;

Sancar, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (27) :25421-25426

[2] Structural basis for FEN-1 substrate specificity and PCNA-mediated activation in DNA replication and repair [J].

Chapados, BR ;

Hosfield, DJ ;

Han, S ;

Qiu, JZ ;

Yelent, B ;

Shen, BH ;

Tainer, JA .

CELL, 2004, 116 (01) :39-50

[3] A proteome chip approach reveals new DNA damage recognition activities in Escherichia coli [J].

Chen, Chien-Sheng ;

Korobkova, Ekaterina ;

Chen, Hao ;

Zhu, Jian ;

Jian, Xing ;

Tao, Sheng-Ce ;

He, Chuan ;

Zhu, Heng .

NATURE METHODS, 2008, 5 (01) :69-74

[4] Who's on first in the cellular response to DNA damage? [J].

Cline, SD ;

Hanawalt, PC .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (05) :361-372

[5] Structures of endonuclease V with DNA reveal initiation of deaminated adenine repair [J].

Dalhus, Bjorn ;

Arvai, Andrew S. ;

Rosnes, Ida ;

Olsen, Oyvind E. ;

Backe, Paul H. ;

Alseth, Ingrun ;

Gao, Honghai ;

Cao, Weiguo ;

Tainer, John A. ;

Bjoras, Magnar .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2009, 16 (02) :138-143

[6] Conserved structural motifs governing the stoichiometric repair of alkylated DNA by O6-alkylguanine-DNA alkyltransferase [J].

Daniels, DS ;

Tainer, JA .

MUTATION RESEARCH-DNA REPAIR, 2000, 460 (3-4) :151-163

[7] Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding [J].

Daniels, DS ;

Mol, CD ;

Arvai, AS ;

Kanugula, S ;

Pegg, AE ;

Tainer, JA .

EMBO JOURNAL, 2000, 19 (07) :1719-1730

[8] DNA binding and nucleotide flipping by the human DNA repair protein AGT [J].

Daniels, DS ;

Woo, TT ;

Luu, KX ;

Noll, DM ;

Clarke, ND ;

Pegg, AE ;

Tainer, JA .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2004, 11 (08) :714-720

[9] The structure of the human AGT protein bound to DNA and its implications for damage detection [J].

Duguid, EM ;

Rice, PA ;

He, C .

JOURNAL OF MOLECULAR BIOLOGY, 2005, 350 (04) :657-666

[10] Expression of the inactive C145A mutant human O6-alkylguanine-DNA alkyltransferase in E-coli increases cell killing and mutations by N-methyl-N′-nitro-N-nitrosoguanidine [J].

Edara, S ;

Kanugula, S ;

Pegg, AE .

CARCINOGENESIS, 1999, 20 (01) :103-108

← 1 2 3 4 5 →