Reaction participants Show >> << Hide
- Name help_outline 5-hydroxymethyl-dUMP Identifier CHEBI:90409 Charge -2 Formula C10H13N2O9P InChIKeyhelp_outline WEBVWKFGRVLCNS-XLPZGREQSA-L SMILEShelp_outline N1([C@@H]2O[C@H](COP([O-])([O-])=O)[C@H](C2)O)C(NC(=O)C(=C1)CO)=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 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 2-deoxy-D-ribose 5-phosphate Identifier CHEBI:62877 Charge -2 Formula C5H9O7P InChIKeyhelp_outline KKZFLSZAWCYPOC-PYHARJCCSA-L SMILEShelp_outline [C@H]1([C@H](CC(O1)O)O)COP([O-])(=O)[O-] 2D coordinates Mol file for the small molecule Search links Involved in 10 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 5-hydroxymethyluracil Identifier CHEBI:16964 (Beilstein: 125482; CAS: 4433-40-3) help_outline Charge 0 Formula C5H6N2O3 InChIKeyhelp_outline JDBGXEHEIRGOBU-UHFFFAOYSA-N SMILEShelp_outline OCc1c[nH]c(=O)[nH]c1=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
Cross-references
| RHEA:77099 | RHEA:77100 | RHEA:77101 | RHEA:77102 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Related reactions help_outline
More general form(s) of this reaction
Publications
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Targeting the nucleotide salvage factor DNPH1 sensitizes BRCA-deficient cells to PARP inhibitors.
Fugger K., Bajrami I., Silva Dos Santos M., Young S.J., Kunzelmann S., Kelly G., Hewitt G., Patel H., Goldstone R., Carell T., Boulton S.J., MacRae J., Taylor I.A., West S.C.
Mutations in the <i>BRCA1</i> or <i>BRCA2</i> tumor suppressor genes predispose individuals to breast and ovarian cancer. In the clinic, these cancers are treated with inhibitors that target poly(ADP-ribose) polymerase (PARP). We show that inhibition of DNPH1, a protein that eliminates cytotoxic n ... >> More
Mutations in the <i>BRCA1</i> or <i>BRCA2</i> tumor suppressor genes predispose individuals to breast and ovarian cancer. In the clinic, these cancers are treated with inhibitors that target poly(ADP-ribose) polymerase (PARP). We show that inhibition of DNPH1, a protein that eliminates cytotoxic nucleotide 5-hydroxymethyl-deoxyuridine (hmdU) monophosphate, potentiates the sensitivity of <i>BRCA</i>-deficient cells to PARP inhibitors (PARPi). Synthetic lethality was mediated by the action of SMUG1 glycosylase on genomic hmdU, leading to PARP trapping, replication fork collapse, DNA break formation, and apoptosis. <i>BRCA1</i>-deficient cells that acquired resistance to PARPi were resensitized by treatment with hmdU and DNPH1 inhibition. Because genomic hmdU is a key determinant of PARPi sensitivity, targeting DNPH1 provides a promising strategy for the hypersensitization of <i>BRCA</i>-deficient cancers to PARPi therapy. << Less
Science 372:156-165(2021) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.