AP endonuclease-independent DNA base excision repair in human cells. 2004

Lee Wiederhold, and John B Leppard, and Padmini Kedar, and Feridoun Karimi-Busheri, and Aghdass Rasouli-Nia, and Michael Weinfeld, and Alan E Tomkinson, and Tadahide Izumi, and Rajendra Prasad, and Samuel H Wilson, and Sankar Mitra, and Tapas K Hazra
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555, USA.

The paradigm for repair of oxidized base lesions in genomes via the base excision repair (BER) pathway is based on studies in Escherichia coli, in which AP endonuclease (APE) removes all 3' blocking groups (including 3' phosphate) generated by DNA glycosylase/AP lyases after base excision. The recently discovered mammalian DNA glycosylase/AP lyases, NEIL1 and NEIL2, unlike the previously characterized OGG1 and NTH1, generate DNA strand breaks with 3' phosphate termini. Here we show that in mammalian cells, removal of the 3' phosphate is dependent on polynucleotide kinase (PNK), and not APE. NEIL1 stably interacts with other BER proteins, DNA polymerase beta (pol beta) and DNA ligase IIIalpha. The complex of NEIL1, pol beta, and DNA ligase IIIalpha together with PNK suggests coordination of NEIL1-initiated repair. That NEIL1/PNK could also repair the products of other DNA glycosylases suggests a broad role for this APE-independent BER pathway in mammals.

UI MeSH Term Description Entries
D011088 DNA Ligases Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC 6.5.1.1 (ATP) and EC 6.5.1.2 (NAD). DNA Joinases,DNA Ligase,Polydeoxyribonucleotide Ligases,Polydeoxyribonucleotide Synthetases,T4 DNA Ligase,DNA Ligase, T4,Joinases, DNA,Ligase, DNA,Ligase, T4 DNA,Ligases, DNA,Ligases, Polydeoxyribonucleotide,Synthetases, Polydeoxyribonucleotide
D011116 Polynucleotide 5'-Hydroxyl-Kinase An enzyme that catalyzes the transfer of a phosphate group to the 5'-terminal hydroxyl groups of DNA and RNA. EC 2.7.1.78. Polynucleotide Hydroxylkinase,Polynucleotide Kinase,5'-Hydroxylpolynucleotide Kinase,DNA 5'-Hydroxylkinase,DNA Kinase,Polynucleotide 5'-Hydroxyl Kinase,Polynucleotide Hydroxykinase,5' Hydroxylpolynucleotide Kinase,5'-Hydroxyl Kinase, Polynucleotide,5'-Hydroxyl-Kinase, Polynucleotide,5'-Hydroxylkinase, DNA,DNA 5' Hydroxylkinase,Hydroxykinase, Polynucleotide,Hydroxylkinase, Polynucleotide,Kinase, 5'-Hydroxylpolynucleotide,Kinase, DNA,Kinase, Polynucleotide,Kinase, Polynucleotide 5'-Hydroxyl,Polynucleotide 5' Hydroxyl Kinase
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072481 DNA Ligase ATP ATP-dependent cellular enzyme which catalyzes DNA replication, repair and recombination through formation of internucleotide ester bonds between phosphate and deoxyribose moieties. Vertebrate cells encode three well-characterized DNA ligases, DNA ligase I, III and IV, all of which are related in structure and sequence. DNA ligases either require ATP or NAD. However, archaebacterial, viral, and some eubacterial DNA ligases are ATP-dependent. ATP-Dependent DNA Ligase,DNA Ligase I,DNA Ligase II,DNA Ligase III,DNA Ligase IIIalpha,DNA Ligase IV,DNA Ligases, ATP-Dependent,LIGIIIalpha Protein,Polydeoxyribonucleotide Synthase ATP,ATP Dependent DNA Ligase,ATP, DNA Ligase,ATP, Polydeoxyribonucleotide Synthase,ATP-Dependent DNA Ligases,DNA Ligase, ATP-Dependent,DNA Ligases, ATP Dependent,IIIalpha, DNA Ligase,Ligase ATP, DNA,Ligase I, DNA,Ligase II, DNA,Ligase III, DNA,Ligase IIIalpha, DNA,Ligase IV, DNA,Ligase, ATP-Dependent DNA,Ligases, ATP-Dependent DNA,Synthase ATP, Polydeoxyribonucleotide
D000075223 Poly-ADP-Ribose Binding Proteins Proteins that contain POLY-ADP RIBOSE BINDING MOTIFS. They include HISTONES and other proteins that function in DNA REPAIR, replication, gene transcription, and APOPTOSIS. pADPr-Binding Proteins,Binding Proteins, Poly-ADP-Ribose,Poly ADP Ribose Binding Proteins,pADPr Binding Proteins
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D043603 DNA-(Apurinic or Apyrimidinic Site) Lyase A DNA repair enzyme that catalyses the excision of ribose residues at apurinic and apyrimidinic DNA sites that can result from the action of DNA GLYCOSYLASES. The enzyme catalyzes a beta-elimination reaction in which the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. This enzyme was previously listed under EC 3.1.25.2. Apurinic DNA Endonuclease,DNA Lyase (Apurinic or Apyrimidinic),Endodeoxyribonuclease (Apurinic or Apyrimidinic),AP Endonuclease,AP Lyase,Apurine-Apyrimidine Endonuclease,Apurinic Endonuclease,Apurine Apyrimidine Endonuclease,DNA Endonuclease, Apurinic,Endonuclease, AP,Endonuclease, Apurine-Apyrimidine,Endonuclease, Apurinic,Endonuclease, Apurinic DNA

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