| Interacting proteins: Q9NUW8 and P11387 |
Pubmed |
SVM Score :0.0 |
| We have previously developed strategies to confer resistance to agents targeting thymidylate synthase ( TS ) and have now expanded our drug resistance strategies to include retroviral expression of tyrosyl DNA phosphodiesterase ( TDP 1 ) , an enzyme recently implicated in the repair of topoisomerase 1 ( Top 1 ) / DNA lesions induced by camptothecin ( CPT ) . ^^^ Hematopoietic progenitor assays of murine bone marrow cells transduced with retroviral vectors encoding TS and TDP 1 showed that bone marrow cells could be protected from the cytotoxic effects of TS and Top 1 inhibition . ^^^ Additionally , this work further illustrated a role for TDP 1 in the repair of dead end Top 1 complexes and implied that TDP 1 expression analysis may aid in predicting the therapeutic effectiveness of the CPT class of compounds . . ^^^ |
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| Interacting proteins: Q9NUW8 and P11387 |
Pubmed |
SVM Score :0.0 |
| Furthermore , targeting DNA repair ( Tdp 1 ) and checkpoints ( ATM , Chk 1 and Chk 2 ) might increase the selectivity of Top 1 inhibitors for tumors , thereby increasing the antitumor activity while reducing the side effects of Top 1 inhibitors . . ^^^ |
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| Interacting proteins: Q9NUW8 and P11387 |
Pubmed |
SVM Score :0.0 |
| Yeast Tdp 1 and Rad 1 Rad10 function as redundant pathways for repairing Top 1 replicative damage . ^^^ Here we report that the tyrosyl DNA phosphodiesterase Tdp 1 and the structure specific endonuclease Rad 1 Rad10 function as primary alternative pathways of Top 1 repair in Saccharomyces cerevisiae . ^^^ Thus , tdp 1 rad1 cells ( including the catalytic point mutant rad 1 D869A ) not only are highly sensitive to the Top 1 poison camptothecin but also exhibit a TOP 1 dependent growth delay . ^^^ |
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| Interacting proteins: Q9NUW8 and P11387 |
Pubmed |
SVM Score :0.0 |
| Despite finding that the yeast Apn 1 protein has a Tdp 1 like biochemical activity , genetic inactivation of all known yeast apurinic endonucleases does not increase the sensitivity of a tdp 1 mutant to direct induction of Top 1 damage . ^^^ In contrast , assays of growth in the presence of the Top 1 poison camptothecin ( CPT ) indicate that the structure specific nucleases dependent on RAD 1 and MUS 81 can contribute independently of TDP 1 to repair , presumably by cutting off a segment of DNA along with the topoisomerase . ^^^ |
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| Interacting proteins: Q9NUW8 and P11387 |
Pubmed |
SVM Score :0.0 |
| However , XRCC 1 complemented cells repaired Top 1 induced DNA breaks faster than XRCC 1 deficient cells , and exhibited enhanced tyrosyl DNA phosphodiesterase ( Tdp 1 ) and polynucleotide kinase phosphatase ( PNKP ) activities . ^^^ XRCC 1 immunoprecipitates contained Tdp 1 polypeptide , and both Tdp 1 and PNKP activities , indicating a functional connection between the XRCC 1 single strand break repair pathway and the repair of Top 1 covalent complexes by Tdp 1 and PNKP . . ^^^ |
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| Interacting proteins: Q9NUW8 and P11387 |
Pubmed |
SVM Score :0.0 |
| In lower eukaryotes , Tdp 1 removes topoisomerase 1 ( top 1 ) peptide from DNA termini during the repair of double strand breaks created by collision of replication forks with top 1 cleavage complexes in proliferating cells . ^^^ Here we show that in human cells TDP 1 is required for repair of chromosomal single strand breaks arising independently of DNA replication from abortive top 1 activity or oxidative stress . ^^^ |
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| Interacting proteins: Q9NUW8 and P11387 |
Pubmed |
SVM Score :0.0 |
| Tyrosyl DNA phosphodiesterase ( Tdp 1 ) can repair Top 1 DNA covalent complexes by hydrolyzing the tyrosyl DNA bond . ^^^ Inhibiting Tdp 1 has the potential to enhance the anticancer activity of Top 1 inhibitors ( http : / / discover . nci . nih . gov / pommier / pommier . htm ) and to act as antiproliferative agents . ^^^ |
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| Interacting proteins: Q9NUW8 and P11387 |
Pubmed |
SVM Score :0.0 |
| Combining tdp 1 mutations with deletions of genes involved in nonhomologous end joining , excision repair , or postreplication repair enhanced sensitivity to Top 2 targeting drugs over the level seen with single mutants , suggesting that Tdp 1 may function in collaboration with multiple pathways involved in strand break repair . tdp 1 mutations can sensitize yeast cells to drugs targeting Top 2 even when TOP 1 is deleted . ^^^ Our results show that Tdp 1 plays more general roles in DNA repair than repair of Top 1 mediated DNA damage , and may participate in repairing many types of base damage to DNA . . ^^^ |
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| Interacting proteins: Q9NUW8 and P11387 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NUW8 and P11387 |
Pubmed |
SVM Score :0.0 |
| NA |
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