PDBsum entry 1de9

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protein dna_rna metals links
Lyase/DNA PDB id
Protein chain
276 a.a. *
_MN ×2
* Residue conservation analysis
PDB id:
Name: Lyase/DNA
Title: Human ape1 endonuclease with bound abasic DNA and mn2+ ion
Structure: 5'-d( Cp Tp Ap C)-3'. Chain: x, u. Engineered: yes. 5'-d(p (3Dr)p Gp Ap Tp C)-3'. Chain: y, v. Engineered: yes. 5'-d( Gp Ap Tp Cp Gp Gp Tp Ap G)-3'. Chain: z, w. Engineered: yes.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
3.00Å     R-factor:   0.183     R-free:   0.274
Authors: C.D.Mol,T.Izumi,S.Mitra,J.A.Tainer
Key ref:
C.D.Mol et al. (2000). DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected] Nature, 403, 451-456. PubMed id: 10667800 DOI: 10.1038/35000249
13-Nov-99     Release date:   02-Feb-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P27695  (APEX1_HUMAN) -  DNA-(apurinic or apyrimidinic site) lyase
318 a.a.
276 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - DNA-(apurinic or apyrimidinic site) lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   1 term 
  Biological process     DNA repair   1 term 
  Biochemical function     DNA binding     3 terms  


DOI no: 10.1038/35000249 Nature 403:451-456 (2000)
PubMed id: 10667800  
DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected]
C.D.Mol, T.Izumi, S.Mitra, J.A.Tainer.
Non-coding apurinic/apyrimidinic (AP) sites in DNA are continually created in cells both spontaneously and by damage-specific DNA glycosylases. The biologically critical human base excision repair enzyme APE1 cleaves the DNA sugar-phosphate backbone at a position 5' of AP sites to prime DNA repair synthesis. Here we report three co-crystal structures of human APE1 bound to abasic DNA which show that APE1 uses a rigid, pre-formed, positively charged surface to kink the DNA helix and engulf the AP-DNA strand. APE1 inserts loops into both the DNA major and minor grooves and binds a flipped-out AP site in a pocket that excludes DNA bases and racemized beta-anomer AP sites. Both the APE1 active-site geometry and a complex with cleaved AP-DNA and Mn2+ support a testable structure-based catalytic mechanism. Alanine substitutions of the residues that penetrate the DNA helix unexpectedly show that human APE1 is structurally optimized to retain the cleaved DNA product. These structural and mutational results show how APE1 probably displaces bound glycosylases and retains the nicked DNA product, suggesting that APE1 acts in vivo to coordinate the orderly transfer of unstable DNA damage intermediates between the excision and synthesis steps of DNA repair.
  Selected figure(s)  
Figure 2.
Figure 2: Stereo views of the APE1 complex with AP-DNA showing double-loop penetration of the DNA helix, plus charge and surface complementarity. a, DNA (top) binding to APE1 (bottom) from the co-crystal structure of APE1 bound to the 11-bp abasic DNA. The complex is viewed from the side that is roughly perpendicular to the kinked DNA helix axis oriented with the AP strand running 5' (left) to 3' (right), and shows the two central, six-stranded APE1 -sheets (orange arrows), - and 3[10] -helices (blue coils), and coils (green tubes). Five APE1 DNA-binding regions (yellow; residues 73-79, 126-129, 174-178, 221-228 and 268-272) contact both the AP-DNA strand (pink carbon polytubes and transparent surface) and the opposing strand (orange polytubes and surface). The position of the divalent metal ion (green sphere) which is 5' of the AP site as derived from the ternary product complex, and the side chains for key residues are shown. b, DNA binding to APE1 viewed looking down on the enzyme-DNA interface, rotated 90^ from the view in a. Arg 177 penetrates the DNA major groove (bottom) and Met 270 inserts through the DNA minor groove (top), capping the DNA-bound APE1 active site. The APE1-bound DNA, which is bent 35^ with the helix axis kinked 5, complements the positively charged DNA-binding surface of APE1, coloured red (-1.5 kT e^ -1) to blue (+1.5 kT e^-1) according to its electrostatic potential (calculated including the Mn2+ ion), which engulfs the AP-DNA strand (pink) around the flipped-out AP site.
Figure 3.
Figure 3: APE1 interactions with the flipped-out AP site provide damage specificity and suggest a specific reaction mechanism for phosphodiester bond cleavage. a, APE1 active-site interactions with the flipped-out abasic deoxyribose and target 5' phosphate. The hydrophobic face of the extrahelical AP site packs within a complementary APE1 pocket formed by the side chains of Phe 166, Trp 280 and Leu 282. The Arg 177 side chain inserts through the kinked DNA major groove to form a hydrogen bond to the non-target AP site 3' phosphate. The target AP site 5' phosphate is oriented by hydrogen bonds with Asn 174, Asn 212 and His 309. Asp 210 is oriented by hydrogen bonds from the Asn 212 backbone amide and Asn 68 N 2. The metal ion position (derived from the ternary product complex) stabilizes the transition state and facilitates the O3' leaving group, perhaps through a first hydration shell water molecule of a Mg2+ion. b, Structure-based reaction mechanism for phosphodiester bond cleavage. Substrate AP-DNA is oriented by the bound divalent metal ion and APE1 active-site residues for attack of an hydroxyl nucleophile activated by buried Asp 210 (left panel). Collapse of the pentacovalent transition state (middle panel) leads to cleavage of the scissile P-O3' bond, with the transition state and O3' leaving group stabilized by the metal ion, leading to bond cleavage and inversion of the phosphate configuration (right panel).
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2000, 403, 451-456) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22237395 D.Fu, J.A.Calvo, and L.D.Samson (2012).
Balancing repair and tolerance of DNA damage caused by alkylating agents.
  Nat Rev Cancer, 12, 104-120.  
23104058 K.Shi, K.Kurahashi, R.Gao, S.E.Tsutakawa, J.A.Tainer, Y.Pommier, and H.Aihara (2012).
Structural basis for recognition of 5'-phosphotyrosine adducts by Tdp2.
  Nat Struct Mol Biol, 19, 1372-1377.
PDB codes: 4f1h 4f1i 4fpv 4fva 4gew
23104055 M.J.Schellenberg, C.D.Appel, S.Adhikari, P.D.Robertson, D.A.Ramsden, and R.S.Williams (2012).
Mechanism of repair of 5'-topoisomerase II-DNA adducts by mammalian tyrosyl-DNA phosphodiesterase 2.
  Nat Struct Mol Biol, 19, 1363-1371.
PDB codes: 4gyz 4gz0 4gz1 4gz2
21353648 D.O.Onyango, A.Naguleswaran, S.Delaplane, A.Reed, M.R.Kelley, M.M.Georgiadis, and W.J.Sullivan (2011).
Base excision repair apurinic/apyrimidinic endonucleases in apicomplexan parasite Toxoplasma gondii.
  DNA Repair (Amst), 10, 466-475.  
20874257 M.R.Kelley, M.Luo, A.Reed, D.Su, S.Delaplane, R.F.Borch, R.L.Nyland, M.L.Gross, and M.M.Georgiadis (2011).
Functional analysis of novel analogues of E3330 that block the redox signaling activity of the multifunctional AP endonuclease/redox signaling enzyme APE1/Ref-1.
  Antioxid Redox Signal, 14, 1387-1401.  
21496641 S.E.Tsutakawa, S.Classen, B.R.Chapados, A.S.Arvai, L.D.Finger, G.Guenther, C.G.Tomlinson, P.Thompson, A.H.Sarker, B.Shen, P.K.Cooper, J.A.Grasby, and J.A.Tainer (2011).
Human flap endonuclease structures, DNA double-base flipping, and a unified understanding of the FEN1 superfamily.
  Cell, 145, 198-211.
PDB codes: 3q8k 3q8l 3q8m
20854710 W.Yang (2011).
Nucleases: diversity of structure, function and mechanism.
  Q Rev Biophys, 44, 1.  
20808930 A.Gelin, M.Redrejo-Rodríguez, J.Laval, O.S.Fedorova, M.Saparbaev, and A.A.Ishchenko (2010).
Genetic and biochemical characterization of human AP endonuclease 1 mutants deficient in nucleotide incision repair activity.
  PLoS One, 5, 0.  
19888678 B.A.Manvilla, K.M.Varney, and A.C.Drohat (2010).
Chemical shift assignments for human apurinic/apyrimidinic endonuclease 1.
  Biomol NMR Assign, 4, 5-8.  
20711647 C.S.Busso, M.W.Lake, and T.Izumi (2010).
Posttranslational modification of mammalian AP endonuclease (APE1).
  Cell Mol Life Sci, 67, 3609-3620.  
20122942 D.Das, D.Moiani, H.L.Axelrod, M.D.Miller, D.McMullan, K.K.Jin, P.Abdubek, T.Astakhova, P.Burra, D.Carlton, H.J.Chiu, T.Clayton, M.C.Deller, L.Duan, D.Ernst, J.Feuerhelm, J.C.Grant, A.Grzechnik, S.K.Grzechnik, G.W.Han, L.Jaroszewski, H.E.Klock, M.W.Knuth, P.Kozbial, S.S.Krishna, A.Kumar, D.Marciano, A.T.Morse, E.Nigoghossian, L.Okach, J.Paulsen, R.Reyes, C.L.Rife, N.Sefcovic, H.J.Tien, C.B.Trame, H.van den Bedem, D.Weekes, Q.Xu, K.O.Hodgson, J.Wooley, M.A.Elsliger, A.M.Deacon, A.Godzik, S.A.Lesley, J.A.Tainer, and I.A.Wilson (2010).
Crystal structure of the first eubacterial Mre11 nuclease reveals novel features that may discriminate substrates during DNA repair.
  J Mol Biol, 397, 647-663.
PDB code: 2q8u
20699270 D.Fantini, C.Vascotto, D.Marasco, C.D'Ambrosio, M.Romanello, L.Vitagliano, C.Pedone, M.Poletto, L.Cesaratto, F.Quadrifoglio, A.Scaloni, J.P.Radicella, and G.Tell (2010).
Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions.
  Nucleic Acids Res, 38, 8239-8256.  
20809131 D.M.Wilson, and A.Simeonov (2010).
Small molecule inhibitors of DNA repair nuclease activities of APE1.
  Cell Mol Life Sci, 67, 3621-3631.  
20927102 E.H.Rubinson, A.S.Gowda, T.E.Spratt, B.Gold, and B.F.Eichman (2010).
An unprecedented nucleic acid capture mechanism for excision of DNA damage.
  Nature, 468, 406-411.
PDB codes: 3jx7 3jxy 3jxz 3jy1
20706766 G.Tell, D.Fantini, and F.Quadrifoglio (2010).
Understanding different functions of mammalian AP endonuclease (APE1) as a promising tool for cancer treatment.
  Cell Mol Life Sci, 67, 3589-3608.  
20628353 H.Wang, M.Morita, X.Yang, T.Suzuki, W.Yang, J.Wang, K.Ito, Q.Wang, C.Zhao, M.Bartlam, T.Yamamoto, and Z.Rao (2010).
Crystal structure of the human CNOT6L nuclease domain reveals strict poly(A) substrate specificity.
  EMBO J, 29, 2566-2576.
PDB codes: 3ngn 3ngo 3ngq
20502938 J.L.Tubbs, and J.A.Tainer (2010).
Alkyltransferase-like proteins: molecular switches between DNA repair pathways.
  Cell Mol Life Sci, 67, 3749-3762.  
20955519 M.Borjigin, B.Martinez, S.Purohit, la Rosa, P.Arenaz, and B.Stec (2010).
Chinese hamster apurinic/apyrimidinic endonuclease (chAPE1) expressed in sf9 cells reveals that its endonuclease activity is regulated by phosphorylation.
  FEBS J, 277, 4732-4740.  
19764832 M.Luo, H.He, M.R.Kelley, and M.M.Georgiadis (2010).
Redox regulation of DNA repair: implications for human health and cancer therapeutic development.
  Antioxid Redox Signal, 12, 1247-1269.  
20675404 R.Tomecki, and A.Dziembowski (2010).
Novel endoribonucleases as central players in various pathways of eukaryotic RNA metabolism.
  RNA, 16, 1692-1724.  
19934257 T.Yamamori, J.DeRicco, A.Naqvi, T.A.Hoffman, I.Mattagajasingh, K.Kasuno, S.B.Jung, C.S.Kim, and K.Irani (2010).
SIRT1 deacetylates APE1 and regulates cellular base excision repair.
  Nucleic Acids Res, 38, 832-845.  
19968858 W.M.Li, T.Barnes, and C.H.Lee (2010).
Endoribonucleases--enzymes gaining spotlight in mRNA metabolism.
  FEBS J, 277, 627-641.  
18715143 A.Bapat, M.L.Fishel, and M.R.Kelley (2009).
Going ape as an approach to cancer therapeutics.
  Antioxid Redox Signal, 11, 651-668.  
19188445 C.Vascotto, D.Fantini, M.Romanello, L.Cesaratto, M.Deganuto, A.Leonardi, J.P.Radicella, M.R.Kelley, C.D'Ambrosio, A.Scaloni, F.Quadrifoglio, and G.Tell (2009).
APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process.
  Mol Cell Biol, 29, 1834-1854.  
18976116 G.Tell, F.Quadrifoglio, C.Tiribelli, and M.R.Kelley (2009).
The many functions of APE1/Ref-1: not only a DNA repair enzyme.
  Antioxid Redox Signal, 11, 601-620.  
19643912 J.L.Harris, B.Jakob, G.Taucher-Scholz, G.L.Dianov, O.J.Becherel, and M.F.Lavin (2009).
Aprataxin, poly-ADP ribose polymerase 1 (PARP-1) and apurinic endonuclease 1 (APE1) function together to protect the genome against oxidative damage.
  Hum Mol Genet, 18, 4102-4117.  
19516334 J.L.Tubbs, V.Latypov, S.Kanugula, A.Butt, M.Melikishvili, R.Kraehenbuehl, O.Fleck, A.Marriott, A.J.Watson, B.Verbeek, G.McGown, M.Thorncroft, M.F.Santibanez-Koref, C.Millington, A.S.Arvai, M.D.Kroeger, L.A.Peterson, D.M.Williams, M.G.Fried, G.P.Margison, A.E.Pegg, and J.A.Tainer (2009).
Flipping of alkylated DNA damage bridges base and nucleotide excision repair.
  Nature, 459, 808-813.
PDB codes: 3gva 3gx4 3gyh
18715144 K.K.Bhakat, A.K.Mantha, and S.Mitra (2009).
Transcriptional regulatory functions of mammalian AP-endonuclease (APE1/Ref-1), an essential multifunctional protein.
  Antioxid Redox Signal, 11, 621-638.  
19188437 M.H.Kim, H.B.Kim, S.Acharya, H.M.Sohn, J.Y.Jun, I.Y.Chang, and H.J.You (2009).
Ape1/Ref-1 induces glial cell-derived neurotropic factor (GDNF) responsiveness by upregulating GDNF receptor alpha1 expression.
  Mol Cell Biol, 29, 2264-2277.  
19671525 N.K.Bernstein, M.Hammel, R.S.Mani, M.Weinfeld, M.Pelikan, J.A.Tainer, and J.N.Glover (2009).
Mechanism of DNA substrate recognition by the mammalian DNA repair enzyme, Polynucleotide Kinase.
  Nucleic Acids Res, 37, 6161-6173.  
19123919 S.T.Mundle, J.C.Delaney, J.M.Essigmann, and P.R.Strauss (2009).
Enzymatic mechanism of human apurinic/apyrimidinic endonuclease against a THF AP site model substrate.
  Biochemistry, 48, 19-26.  
19181704 V.M.Castillo-Acosta, L.M.Ruiz-Pérez, W.Yang, D.González-Pacanowska, and A.E.Vidal (2009).
Identification of a residue critical for the excision of 3'-blocking ends in apurinic/apyrimidinic endonucleases of the Xth family.
  Nucleic Acids Res, 37, 1829-1842.  
18437203 A.Abyzov, A.Uzun, P.R.Strauss, and V.A.Ilyin (2008).
An AP endonuclease 1-DNA polymerase beta complex: theoretical prediction of interacting surfaces.
  PLoS Comput Biol, 4, e1000066.  
18436236 A.K.Mantha, N.Oezguen, K.K.Bhakat, T.Izumi, W.Braun, and S.Mitra (2008).
Unusual role of a cysteine residue in substrate binding and activity of human AP-endonuclease 1.
  J Mol Biol, 379, 28-37.  
18576638 A.S.Lipton, R.W.Heck, S.Primak, D.R.McNeill, D.M.Wilson, and P.D.Ellis (2008).
Characterization of Mg2+ binding to the DNA repair protein apurinic/apyrimidic endonuclease 1 via solid-state 25Mg NMR spectroscopy.
  J Am Chem Soc, 130, 9332-9341.  
18408731 E.D.Garcin, D.J.Hosfield, S.A.Desai, B.J.Haas, M.Björas, R.P.Cunningham, and J.A.Tainer (2008).
DNA apurinic-apyrimidinic site binding and excision by endonuclease IV.
  Nat Struct Mol Biol, 15, 515-522.
PDB codes: 2nq9 2nqh 2nqj
18072751 J.C.Delaney, and J.M.Essigmann (2008).
Biological properties of single chemical-DNA adducts: a twenty year perspective.
  Chem Res Toxicol, 21, 232-252.  
18025040 J.Chen, F.Y.Dupradeau, D.A.Case, C.J.Turner, and J.Stubbe (2008).
DNA oligonucleotides with A, T, G or C opposite an abasic site: structure and dynamics.
  Nucleic Acids Res, 36, 253-262.
PDB codes: 2o7w 2o7x 2o7y 2o7z 2o80 2o82
18313385 J.L.Parsons, P.S.Tait, D.Finch, I.I.Dianova, S.L.Allinson, and G.L.Dianov (2008).
CHIP-mediated degradation and DNA damage-dependent stabilization regulate base excision repair proteins.
  Mol Cell, 29, 477-487.  
18626472 K.W.Caldecott (2008).
Single-strand break repair and genetic disease.
  Nat Rev Genet, 9, 619-631.  
18042731 L.A.Seiple, J.H.Cardellina, R.Akee, and J.T.Stivers (2008).
Potent inhibition of human apurinic/apyrimidinic endonuclease 1 by arylstibonic acids.
  Mol Pharmacol, 73, 669-677.  
18805789 M.E.Fitzgerald, and A.C.Drohat (2008).
  J Biol Chem, 283, 32680-32690.  
18166975 M.L.Hegde, T.K.Hazra, and S.Mitra (2008).
Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells.
  Cell Res, 18, 27-47.  
18515104 M.X.Li, D.Wang, Z.Y.Zhong, D.B.Xiang, Z.P.Li, J.Y.Xie, Z.Z.Yang, F.Jin, and Y.Qing (2008).
Targeting truncated APE1 in mitochondria enhances cell survival after oxidative stress.
  Free Radic Biol Med, 45, 592-601.  
18809583 R.Chattopadhyay, S.Das, A.K.Maiti, I.Boldogh, J.Xie, T.K.Hazra, K.Kohno, S.Mitra, and K.K.Bhakat (2008).
Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1.
  Mol Cell Biol, 28, 7066-7080.  
18025089 S.Adhikari, A.Uren, and R.Roy (2008).
Dipole-dipole interaction stabilizes the transition state of apurinic/apyrimidinic endonuclease--abasic site interaction.
  J Biol Chem, 283, 1334-1339.  
18157156 W.Yang (2008).
Structure and mechanism for DNA lesion recognition.
  Cell Res, 18, 184-197.  
17318183 E.P.Carpenter, A.Corbett, H.Thomson, J.Adacha, K.Jensen, J.Bergeron, I.Kasampalidis, R.Exley, M.Winterbotham, C.Tang, G.S.Baldwin, and P.Freemont (2007).
AP endonuclease paralogues with distinct activities in DNA repair and bacterial pathogenesis.
  EMBO J, 26, 1363-1372.
PDB codes: 2jc4 2jc5
17617640 G.Tamulaitis, M.Zaremba, R.H.Szczepanowski, M.Bochtler, and V.Siksnys (2007).
Nucleotide flipping by restriction enzymes analyzed by 2-aminopurine steady-state fluorescence.
  Nucleic Acids Res, 35, 4792-4799.  
17567611 H.K.Wong, M.Muftuoglu, G.Beck, S.Z.Imam, V.A.Bohr, and D.M.Wilson (2007).
Cockayne syndrome B protein stimulates apurinic endonuclease 1 activity and protects against agents that introduce base excision repair intermediates.
  Nucleic Acids Res, 35, 4103-4113.  
17485252 J.L.Tubbs, A.E.Pegg, and J.A.Tainer (2007).
DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair by O6-alkylguanine-DNA alkyltransferase and its implications for cancer chemotherapy.
  DNA Repair (Amst), 6, 1100-1115.  
17626046 K.Repanas, N.Zingler, L.E.Layer, G.G.Schumann, A.Perrakis, and O.Weichenrieder (2007).
Determinants for DNA target structure selectivity of the human LINE-1 retrotransposon endonuclease.
  Nucleic Acids Res, 35, 4914-4926.
PDB codes: 2v0r 2v0s
17699520 K.Rogers, G.Gao, and L.Simpson (2007).
Uridylate-specific 3' 5'-exoribonucleases involved in uridylate-deletion RNA editing in trypanosomatid mitochondria.
  J Biol Chem, 282, 29073-29080.  
17218168 L.F.Melo, S.T.Mundle, M.H.Fattal, N.E.O'Regan, and P.R.Strauss (2007).
Role of active site tyrosines in dynamic aspects of DNA binding by AP endonuclease.
  DNA Repair (Amst), 6, 374-382.  
17537809 N.Maita, H.Aoyagi, M.Osanai, M.Shirakawa, and H.Fujiwara (2007).
Characterization of the sequence specificity of the R1Bm endonuclease domain by structural and biochemical studies.
  Nucleic Acids Res, 35, 3918-3927.
PDB code: 2ei9
17724035 R.L.Maher, and L.B.Bloom (2007).
Pre-steady-state kinetic characterization of the AP endonuclease activity of human AP endonuclease 1.
  J Biol Chem, 282, 30577-30585.  
17576692 S.Nakanishi, R.Prasad, S.H.Wilson, and M.Smerdon (2007).
Different structural states in oligonucleosomes are required for early versus late steps of base excision repair.
  Nucleic Acids Res, 35, 4313-4321.  
17855402 X.Guan, A.Madabushi, D.Y.Chang, M.E.Fitzgerald, G.Shi, A.C.Drohat, and A.L.Lu (2007).
The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates DNA repair enzyme TDG glycosylase.
  Nucleic Acids Res, 35, 6207-6218.  
17395641 X.Guan, H.Bai, G.Shi, C.A.Theriot, T.K.Hazra, S.Mitra, and A.L.Lu (2007).
The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase.
  Nucleic Acids Res, 35, 2463-2472.  
16506094 I.Jagannathan, H.A.Cole, and J.J.Hayes (2006).
Base excision repair in nucleosome substrates.
  Chromosome Res, 14, 27-37.  
16780580 I.S.Mian, E.A.Worthey, and R.Salavati (2006).
Taking U out, with two nucleases?
  BMC Bioinformatics, 7, 305.  
16540594 K.Kaneda, J.Sekiguchi, and T.Shida (2006).
Role of the tryptophan residue in the vicinity of the catalytic center of exonuclease III family AP endonucleases: AP site recognition mechanism.
  Nucleic Acids Res, 34, 1552-1563.  
16960376 K.Kaneda, K.Ohishi, J.Sekiguchi, and T.Shida (2006).
Characterization of the AP endonucleases from Thermoplasma volcanium and Lactobacillus plantarum: Contributions of two important tryptophan residues to AP site recognition.
  Biosci Biotechnol Biochem, 70, 2213-2221.  
16397295 N.Lévy, A.Martz, A.Bresson, C.Spenlehauer, Murcia, and J.Ménissier-de Murcia (2006).
XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA damage.
  Nucleic Acids Res, 34, 32-41.  
16687656 P.Burkovics, V.Szukacsov, I.Unk, and L.Haracska (2006).
Human Ape2 protein has a 3'-5' exonuclease activity that acts preferentially on mismatched base pairs.
  Nucleic Acids Res, 34, 2508-2515.  
16617147 R.Chattopadhyay, L.Wiederhold, B.Szczesny, I.Boldogh, T.K.Hazra, T.Izumi, and S.Mitra (2006).
Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells.
  Nucleic Acids Res, 34, 2067-2076.  
16966376 Y.Wang, C.C.Shupenko, L.F.Melo, and P.R.Strauss (2006).
DNA repair protein involved in heart and blood development.
  Mol Cell Biol, 26, 9083-9093.  
15533944 D.Y.Chang, and A.L.Lu (2005).
Interaction of checkpoint proteins Hus1/Rad1/Rad9 with DNA base excision repair enzyme MutY homolog in fission yeast, Schizosaccharomyces pombe.
  J Biol Chem, 280, 408-417.  
15942031 E.B.Jackson, C.A.Theriot, R.Chattopadhyay, S.Mitra, and T.Izumi (2005).
Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1).
  Nucleic Acids Res, 33, 3303-3312.  
16279940 J.L.Parsons, I.I.Dianova, E.Boswell, M.Weinfeld, and G.L.Dianov (2005).
End-damage-specific proteins facilitate recruitment or stability of X-ray cross-complementing protein 1 at the sites of DNA single-strand break repair.
  FEBS J, 272, 5753-5763.  
15606310 M.E.Lomax, H.Salje, S.Cunniffe, and P.O'Neill (2005).
8-OxoA inhibits the incision of an AP site by the DNA glycosylases Fpg, Nth and the AP endonuclease HAP1.
  Radiat Res, 163, 79-84.  
16113242 S.Madhusudan, F.Smart, P.Shrimpton, J.L.Parsons, L.Gardiner, S.Houlbrook, D.C.Talbot, T.Hammonds, P.A.Freemont, M.J.Sternberg, G.L.Dianov, and I.D.Hickson (2005).
Isolation of a small molecule inhibitor of DNA base excision repair.
  Nucleic Acids Res, 33, 4711-4724.  
16199493 S.Sen, N.A.Paraggio, L.A.Gearheart, E.E.Connor, A.Issa, R.S.Coleman, D.M.Wilson, M.D.Wyatt, and M.A.Berg (2005).
Effect of protein binding on ultrafast DNA dynamics: characterization of a DNA:APE1 complex.
  Biophys J, 89, 4129-4138.  
15824325 T.Izumi, D.B.Brown, C.V.Naidu, K.K.Bhakat, M.A.Macinnes, H.Saito, D.J.Chen, and S.Mitra (2005).
Two essential but distinct functions of the mammalian abasic endonuclease.
  Proc Natl Acad Sci U S A, 102, 5739-5743.  
15755742 U.Gioia, P.Laneve, M.Dlakic, M.Arceci, I.Bozzoni, and E.Caffarelli (2005).
Functional characterization of XendoU, the endoribonuclease involved in small nucleolar RNA biosynthesis.
  J Biol Chem, 280, 18996-19002.  
15908697 X.P.Zhang, K.I.Lee, J.A.Solinger, K.Kiianitsa, and W.D.Heyer (2005).
Gly-103 in the N-terminal domain of Saccharomyces cerevisiae Rad51 protein is critical for DNA binding.
  J Biol Chem, 280, 26303-26311.  
15155853 A.B.Guliaev, B.Hang, and B.Singer (2004).
Structural insights by molecular dynamics simulations into specificity of the major human AP endonuclease toward the benzene-derived DNA adduct, pBQ-C.
  Nucleic Acids Res, 32, 2844-2852.  
15385537 B.Ahn, J.A.Harrigan, F.E.Indig, D.M.Wilson, and V.A.Bohr (2004).
Regulation of WRN helicase activity in human base excision repair.
  J Biol Chem, 279, 53465-53474.  
15499577 B.Hang (2004).
Repair of exocyclic DNA adducts: rings of complexity.
  Bioessays, 26, 1195-1208.  
  15159209 D.R.McNeill, A.Narayana, H.K.Wong, and D.M.Wilson (2004).
Inhibition of Ape1 nuclease activity by lead, iron, and cadmium.
  Environ Health Perspect, 112, 799-804.  
15221026 D.S.Daniels, T.T.Woo, K.X.Luu, D.M.Noll, N.D.Clarke, A.E.Pegg, and J.A.Tainer (2004).
DNA binding and nucleotide flipping by the human DNA repair protein AGT.
  Nat Struct Mol Biol, 11, 714-720.
PDB codes: 1t38 1t39
15078879 D.Wong, and B.Demple (2004).
Modulation of the 5'-deoxyribose-5-phosphate lyase and DNA synthesis activities of mammalian DNA polymerase beta by apurinic/apyrimidinic endonuclease 1.
  J Biol Chem, 279, 25268-25275.  
15310837 H.Ma, H.M.Lee, and E.W.Englander (2004).
N-terminus of the rat adenine glycosylase MYH affects excision rates and processing of MYH-generated abasic sites.
  Nucleic Acids Res, 32, 4332-4339.  
15141024 I.I.Dianova, K.M.Sleeth, S.L.Allinson, J.L.Parsons, C.Breslin, K.W.Caldecott, and G.L.Dianov (2004).
XRCC1-DNA polymerase beta interaction is required for efficient base excision repair.
  Nucleic Acids Res, 32, 2550-2555.  
14704345 L.Gros, A.A.Ishchenko, H.Ide, R.H.Elder, and M.K.Saparbaev (2004).
The major human AP endonuclease (Ape1) is involved in the nucleotide incision repair pathway.
  Nucleic Acids Res, 32, 73-81.  
15178685 L.Larivière, and S.Moréra (2004).
Structural evidence of a passive base-flipping mechanism for beta-glucosyltransferase.
  J Biol Chem, 279, 34715-34720.
PDB codes: 1sxp 1sxq
15479784 M.Akbari, M.Otterlei, J.Peña-Diaz, P.A.Aas, B.Kavli, N.B.Liabakk, L.Hagen, K.Imai, A.Durandy, G.Slupphaug, and H.E.Krokan (2004).
Repair of U/G and U/A in DNA by UNG2-associated repair complexes takes place predominantly by short-patch repair both in proliferating and growth-arrested cells.
  Nucleic Acids Res, 32, 5486-5498.  
15155847 N.B.Edfeldt, E.A.Harwood, S.T.Sigurdsson, P.B.Hopkins, and B.R.Reid (2004).
Solution structure of a nitrous acid induced DNA interstrand cross-link.
  Nucleic Acids Res, 32, 2785-2794.
PDB codes: 1s9n 1s9o
15459284 N.G.Beloglazova, O.O.Kirpota, K.V.Starostin, A.A.Ishchenko, V.I.Yamkovoy, D.O.Zharkov, K.T.Douglas, and G.A.Nevinsky (2004).
Thermodynamic, kinetic and structural basis for recognition and repair of abasic sites in DNA by apurinic/apyrimidinic endonuclease from human placenta.
  Nucleic Acids Res, 32, 5134-5146.  
15247245 N.Maita, T.Anzai, H.Aoyagi, H.Mizuno, and H.Fujiwara (2004).
Crystal structure of the endonuclease domain encoded by the telomere-specific long interspersed nuclear element, TRAS1.
  J Biol Chem, 279, 41067-41076.
PDB code: 1wdu
15274918 O.Weichenrieder, K.Repanas, and A.Perrakis (2004).
Crystal structure of the targeting endonuclease of the human LINE-1 retrotransposon.
  Structure, 12, 975-986.
PDB code: 1vyb
12799467 B.C.Beard, S.H.Wilson, and M.J.Smerdon (2003).
Suppressed catalytic activity of base excision repair enzymes on rotationally positioned uracil in nucleosomes.
  Proc Natl Acad Sci U S A, 100, 7465-7470.  
12519758 D.R.Marenstein, M.K.Chan, A.Altamirano, A.K.Basu, R.J.Boorstein, R.P.Cunningham, and G.W.Teebor (2003).
Substrate specificity of human endonuclease III (hNTH1). Effect of human APE1 on hNTH1 activity.
  J Biol Chem, 278, 9005-9012.  
12857737 D.Wong, M.S.DeMott, and B.Demple (2003).
Modulation of the 3'-->5'-exonuclease activity of human apurinic endonuclease (Ape1) by its 5'-incised Abasic DNA product.
  J Biol Chem, 278, 36242-36249.  
14602897 E.A.Worthey, A.Schnaufer, I.S.Mian, K.Stuart, and R.Salavati (2003).
Comparative analysis of editosome proteins in trypanosomatids.
  Nucleic Acids Res, 31, 6392-6408.  
12966083 J.C.Shen, and L.A.Loeb (2003).
Mutations in the alpha8 loop of human APE1 alter binding and cleavage of DNA containing an abasic site.
  J Biol Chem, 278, 46994-47001.  
14633989 K.K.Bhakat, T.Izumi, S.H.Yang, T.K.Hazra, and S.Mitra (2003).
Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene.
  EMBO J, 22, 6299-6309.  
12624104 K.M.Chou, and Y.C.Cheng (2003).
The exonuclease activity of human apurinic/apyrimidinic endonuclease (APE1). Biochemical properties and inhibition by the natural dinucleotide Gp4G.
  J Biol Chem, 278, 18289-18296.  
12682353 M.C.Hall, P.V.Shcherbakova, J.M.Fortune, C.H.Borchers, J.M.Dial, K.B.Tomer, and T.A.Kunkel (2003).
DNA binding by yeast Mlh1 and Pms1: implications for DNA mismatch repair.
  Nucleic Acids Res, 31, 2025-2034.  
12590136 P.Viswanathan, J.Chen, Y.C.Chiang, and C.L.Denis (2003).
Identification of multiple RNA features that influence CCR4 deadenylation activity.
  J Biol Chem, 278, 14949-14955.  
14500814 S.F.El-Khamisy, M.Masutani, H.Suzuki, and K.W.Caldecott (2003).
A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage.
  Nucleic Acids Res, 31, 5526-5533.  
12734201 T.Matsuda, B.J.Vande Berg, K.Bebenek, W.P.Osheroff, S.H.Wilson, and T.A.Kunkel (2003).
The base substitution fidelity of DNA polymerase beta-dependent single nucleotide base excision repair.
  J Biol Chem, 278, 25947-25951.  
14522981 X.Liu, S.Choudhury, and R.Roy (2003).
In vitro and in vivo dimerization of human endonuclease III stimulates its activity.
  J Biol Chem, 278, 50061-50069.  
12453426 C.F.Huggins, D.R.Chafin, S.Aoyagi, L.A.Henricksen, R.A.Bambara, and J.J.Hayes (2002).
Flap endonuclease 1 efficiently cleaves base excision repair and DNA replication intermediates assembled into nucleosomes.
  Mol Cell, 10, 1201-1211.  
12445335 C.H.Schein, N.Ozgün, T.Izumi, and W.Braun (2002).
Total sequence decomposition distinguishes functional modules, "molegos" in apurinic/apyrimidinic endonucleases.
  BMC Bioinformatics, 3, 37.  
12490718 H.D.Junker, S.T.Hoehn, R.C.Bunt, V.Marathius, J.Chen, C.J.Turner, and J.Stubbe (2002).
Synthesis, characterization and solution structure of tethered oligonucleotides containing an internal 3'-phosphoglycolate, 5'-phosphate gapped lesion.
  Nucleic Acids Res, 30, 5497-5508.
PDB codes: 1g5k 1gj1 1n0k 1n0o
11889047 J.Chen, Y.C.Chiang, and C.L.Denis (2002).
CCR4, a 3'-5' poly(A) RNA and ssDNA exonuclease, is the catalytic component of the cytoplasmic deadenylase.
  EMBO J, 21, 1414-1426.  
12081482 J.Huang, J.Lu, F.Barany, and W.Cao (2002).
Mutational analysis of endonuclease V from Thermotoga maritima.
  Biochemistry, 41, 8342-8350.  
11960995 M.A.Pope, S.L.Porello, and S.S.David (2002).
Escherichia coli apurinic-apyrimidinic endonucleases enhance the turnover of the adenine glycosylase MutY with G:A substrates.
  J Biol Chem, 277, 22605-22615.  
12086678 S.Mitra, T.Izumi, I.Boldogh, K.K.Bhakat, J.W.Hill, and T.K.Hazra (2002).
Choreography of oxidative damage repair in mammalian genomes.
  Free Radic Biol Med, 33, 15-28.  
12200445 T.A.Ranalli, S.Tom, and R.A.Bambara (2002).
AP endonuclease 1 coordinates flap endonuclease 1 and DNA ligase I activity in long patch base excision repair.
  J Biol Chem, 277, 41715-41724.  
11889051 U.Hardeland, R.Steinacher, J.Jiricny, and P.Schär (2002).
Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover.
  EMBO J, 21, 1456-1464.  
11948190 V.Schreiber, J.C.Amé, P.Dollé, I.Schultz, B.Rinaldi, V.Fraulob, J.Ménissier-de Murcia, and Murcia (2002).
Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1.
  J Biol Chem, 277, 23028-23036.  
11707423 A.E.Vidal, S.Boiteux, I.D.Hickson, and J.P.Radicella (2001).
XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions.
  EMBO J, 20, 6530-6539.  
11170398 A.J.Podlutsky, I.I.Dianova, S.H.Wilson, V.A.Bohr, and G.L.Dianov (2001).
DNA synthesis and dRPase activities of polymerase beta are both essential for single-nucleotide patch base excision repair in mammalian cell extracts.
  Biochemistry, 40, 809-813.  
11317342 A.Ronen, and B.W.Glickman (2001).
Human DNA repair genes.
  Environ Mol Mutagen, 37, 241-283.  
11264462 C.J.Norbury, and I.D.Hickson (2001).
Cellular responses to DNA damage.
  Annu Rev Pharmacol Toxicol, 41, 367-401.  
11163244 C.J.Whitehouse, R.M.Taylor, A.Thistlethwaite, H.Zhang, F.Karimi-Busheri, D.D.Lasko, M.Weinfeld, and K.W.Caldecott (2001).
XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair.
  Cell, 104, 107-117.  
11170417 E.L.Rachofsky, E.Seibert, J.T.Stivers, R.Osman, and J.B.Ross (2001).
Conformation and dynamics of abasic sites in DNA investigated by time-resolved fluorescence of 2-aminopurine.
  Biochemistry, 40, 957-967.  
11494323 G.L.Dianov, P.O'Neill, and D.T.Goodhead (2001).
Securing genome stability by orchestrating DNA repair: removal of radiation-induced clustered lesions in DNA.
  Bioessays, 23, 745-749.  
11483530 H.Nilsen, K.A.Haushalter, P.Robins, D.E.Barnes, G.L.Verdine, and T.Lindahl (2001).
Excision of deaminated cytosine from the vertebrate genome: role of the SMUG1 uracil-DNA glycosylase.
  EMBO J, 20, 4278-4286.  
11160897 H.Yang, W.M.Clendenin, D.Wong, B.Demple, M.M.Slupska, J.H.Chiang, and J.H.Miller (2001).
Enhanced activity of adenine-DNA glycosylase (Myh) by apurinic/apyrimidinic endonuclease (Ape1) in mammalian base excision repair of an A/GO mismatch.
  Nucleic Acids Res, 29, 743-752.  
11238902 I.Unk, L.Haracska, S.Prakash, and L.Prakash (2001).
3'-phosphodiesterase and 3'-->5' exonuclease activities of yeast Apn2 protein and requirement of these activities for repair of oxidative DNA damage.
  Mol Cell Biol, 21, 1656-1661.  
11139613 J.W.Hill, T.K.Hazra, T.Izumi, and S.Mitra (2001).
Stimulation of human 8-oxoguanine-DNA glycosylase by AP-endonuclease: potential coordination of the initial steps in base excision repair.
  Nucleic Acids Res, 29, 430-438.  
11371344 K.P.Hopfner, A.Karcher, L.Craig, T.T.Woo, J.P.Carney, and J.A.Tainer (2001).
Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase.
  Cell, 105, 473-485.
PDB codes: 1ii7 1ii8
11340626 K.W.Caldecott (2001).
Mammalian DNA single-strand break repair: an X-ra(y)ted affair.
  Bioessays, 23, 447-455.  
11223884 O.D.Schärer, and J.Jiricny (2001).
Recent progress in the biology, chemistry and structural biology of DNA glycosylases.
  Bioessays, 23, 270-281.  
11557809 S.E.Tsutakawa, and K.Morikawa (2001).
The structural basis of damaged DNA recognition and endonucleolytic cleavage for very short patch repair endonuclease.
  Nucleic Acids Res, 29, 3775-3783.  
11726527 S.L.Allinson, I.I.Dianova, and G.L.Dianov (2001).
DNA polymerase beta is the major dRP lyase involved in repair of oxidative base lesions in DNA by mammalian cell extracts.
  EMBO J, 20, 6919-6926.  
11746753 S.Mitra, I.Boldogh, T.Izumi, and T.K.Hazra (2001).
Complexities of the DNA base excision repair pathway for repair of oxidative DNA damage.
  Environ Mol Mutagen, 38, 180-190.  
11504879 S.T.Hoehn, C.J.Turner, and J.Stubbe (2001).
Solution structure of an oligonucleotide containing an abasic site: evidence for an unusual deoxyribose conformation.
  Nucleic Acids Res, 29, 3413-3423.
PDB codes: 1g5d 1g5e 1giz 1gj0
11514661 W.A.Breyer, and B.W.Matthews (2001).
A structural basis for processivity.
  Protein Sci, 10, 1699-1711.  
11557810 X.Cheng, and R.J.Roberts (2001).
AdoMet-dependent methylation, DNA methyltransferases and base flipping.
  Nucleic Acids Res, 29, 3784-3795.  
11348594 Y.Tsujishita, S.Guo, L.E.Stolz, J.D.York, and J.H.Hurley (2001).
Specificity determinants in phosphoinositide dephosphorylation: crystal structure of an archetypal inositol polyphosphate 5-phosphatase.
  Cell, 105, 379-389.
PDB codes: 1i9y 1i9z
10773072 A.Marintchev, A.Robertson, E.K.Dimitriadis, R.Prasad, S.H.Wilson, and G.P.Mullen (2000).
Domain specific interaction in the XRCC1-DNA polymerase beta complex.
  Nucleic Acids Res, 28, 2049-2059.  
10871413 D.Barsky, N.Foloppe, S.Ahmadia, D.M.Wilson, and A.D.MacKerell (2000).
New insights into the structure of abasic DNA from molecular dynamics simulations.
  Nucleic Acids Res, 28, 2613-2626.  
10871340 D.G.Rothwell, B.Hang, M.A.Gorman, P.S.Freemont, B.Singer, and I.D.Hickson (2000).
Substitution of Asp-210 in HAP1 (APE/Ref-1) eliminates endonuclease activity but stabilises substrate binding.
  Nucleic Acids Res, 28, 2207-2213.  
10912000 H.Nilsen, I.Rosewell, P.Robins, C.F.Skjelbred, S.Andersen, G.Slupphaug, G.Daly, H.E.Krokan, T.Lindahl, and D.E.Barnes (2000).
Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication.
  Mol Cell, 5, 1059-1065.  
12760026 K.P.Hopfner, S.S.Parikh, and J.A.Tainer (2000).
Envisioning the fourth dimension of the genetic code: the structural biology of macromolecular recognition and conformational switching in DNA repair.
  Cold Spring Harb Symp Quant Biol, 65, 113-126.  
11152564 M.Z.Hadi, and D.M.Wilson (2000).
Second human protein with homology to the Escherichia coli abasic endonuclease exonuclease III.
  Environ Mol Mutagen, 36, 312-324.  
11024165 M.Z.Hadi, M.A.Coleman, K.Fidelis, H.W.Mohrenweiser, and D.M.Wilson (2000).
Functional characterization of Ape1 variants identified in the human population.
  Nucleic Acids Res, 28, 3871-3879.  
10805771 S.S.Parikh, G.Walcher, G.D.Jones, G.Slupphaug, H.E.Krokan, G.M.Blackburn, and J.A.Tainer (2000).
Uracil-DNA glycosylase-DNA substrate and product structures: conformational strain promotes catalytic efficiency by coupled stereoelectronic effects.
  Proc Natl Acad Sci U S A, 97, 5083-5088.
PDB codes: 1emh 1emj
12760027 T.Lindahl, and D.E.Barnes (2000).
Repair of endogenous DNA damage.
  Cold Spring Harb Symp Quant Biol, 65, 127-133.  
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