Enzymes
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Namehelp_outline
a 3'-end 2'-deoxyribonucleotide-(2,3-dehydro-2,3-deoxyribose 5'-phosphate)-DNA
Identifier
RHEA-COMP:16897
Reactive part
help_outline
- Name help_outline 3'-end deoxyribonucleotide 2,3-dehydro-2,3-deoxyribose phosphate residue Identifier CHEBI:157695 Charge -2 Formula C10H14O10P2R SMILEShelp_outline *[C@@H]1O[C@H](COP(*)(=O)[O-])[C@H](C1)OP(OC[C@@H](O)/C=C/C=O)([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline (2E,4S)-4,5-dihydroxypent-2-enal Identifier CHEBI:157706 Charge 0 Formula C5H8O3 InChIKeyhelp_outline MERWVFZVBUHPAV-WYPBCBNTSA-N SMILEShelp_outline OC[C@H](/C=C/C=O)O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
a 3'end (2'-deoxyribonucleotide 3'-phosphate)-DNA
Identifier
RHEA-COMP:13864
Reactive part
help_outline
- Name help_outline 3'-end deoxyribonucleotide 3'-phosphate residue Identifier CHEBI:138147 Charge -3 Formula C5H7O8P2R SMILEShelp_outline *[C@@H]1O[C@H](COP(*)(=O)[O-])[C@H](C1)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:65764 | RHEA:65765 | RHEA:65766 | RHEA:65767 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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| Gene Ontology help_outline |
Publications
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AP-site cleavage activity of tyrosyl-DNA phosphodiesterase 1.
Lebedeva N.A., Rechkunova N.I., Lavrik O.I.
APE-independent base excision repair (BER) pathway plays an important role in the regulation of DNA repair mechanisms. In this study it has been found that recently discovered tyrosyl-DNA phosphodiesterase 1 (Tdp1) catalyzes the AP site cleavage reaction to generate breaks with the 3'- and 5'-phos ... >> More
APE-independent base excision repair (BER) pathway plays an important role in the regulation of DNA repair mechanisms. In this study it has been found that recently discovered tyrosyl-DNA phosphodiesterase 1 (Tdp1) catalyzes the AP site cleavage reaction to generate breaks with the 3'- and 5'-phosphate termini. The removal of the 3'-phosphate is performed by polynucleotide kinase phosphatase (PNKP). Tdp1 is known to interact stably with BER proteins: DNA polymerase beta (Pol β), XRCC1, PARP1 and DNA ligase III. The data suggest a role of Tdp1 in the new APE-independent BER pathway in mammals. << Less
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Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damage induced by topoisomerases I and II and base alkylation in vertebrate cells.
Murai J., Huang S.Y., Das B.B., Dexheimer T.S., Takeda S., Pommier Y.
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs topoisomerase I cleavage complexes (Top1cc) by hydrolyzing their 3'-phosphotyrosyl DNA bonds and repairs bleomycin-induced DNA damage by hydrolyzing 3'-phosphoglycolates. Yeast Tdp1 has also been implicated in the repair of topoisomerase II-DNA cleava ... >> More
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs topoisomerase I cleavage complexes (Top1cc) by hydrolyzing their 3'-phosphotyrosyl DNA bonds and repairs bleomycin-induced DNA damage by hydrolyzing 3'-phosphoglycolates. Yeast Tdp1 has also been implicated in the repair of topoisomerase II-DNA cleavage complexes (Top2cc). To determine whether vertebrate Tdp1 is involved in the repair of various DNA end-blocking lesions, we generated Tdp1 knock-out cells in chicken DT40 cells (Tdp1-/-) and Tdp1-complemented DT40 cells with human TDP1. We found that Tdp1-/-cells were not only hypersensitive to camptothecin and bleomycin but also to etoposide, methyl methanesulfonate (MMS), H(2)O(2), and ionizing radiation. We also show they were deficient in mitochondrial Tdp1 activity. In biochemical assays, recombinant human TDP1 was found to process 5'-phosphotyrosyl DNA ends when they mimic the 5'-overhangs of Top2cc. Tdp1 also processes 3'-deoxyribose phosphates generated from hydrolysis of abasic sites, which is consistent with the hypersensitivity of Tdp1-/-cells to MMS and H(2)O(2). Because recent studies established that CtIP together with BRCA1 also repairs topoisomerase-mediated DNA damage, we generated dual Tdp1-CtIP-deficient DT40 cells. Our results show that Tdp1 and CtIP act in parallel pathways for the repair of Top1cc and MMS-induced lesions but are epistatic for Top2cc. Together, our findings reveal a broad involvement of Tdp1 in DNA repair and clarify the role of human TDP1 in the repair of Top2-induced DNA damage. << Less
J Biol Chem 287:12848-12857(2012) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.