ArticlePloS one2010
MRE11 function in response to topoisomerase poisons is independent of its function in double-strand break repair in Saccharomyces cerevisiae.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Trial
- Article
- Yeast-based screening of cancer mutations in the DNA damage response protein Mre11 demonstrates importance of conserved capping domain residues.Molecular biology reports · 2021Article
- Small Molecule Inhibitors Confirm Ubiquitin-Dependent Removal of TOP2-DNA Covalent Complexes.Molecular pharmacology · 2020Article
- Excision repair of topoisomerase DNA-protein crosslinks (TOP-DPC).DNA repair · 2020Review
- Deletions associated with stabilization of the Top1 cleavage complex in yeast are products of the nonhomologous end-joining pathway.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A nucleotide resolution map of Top2-linked DNA breaks in the yeast and human genome.Nature communications · 2019Article
- Apn2 resolves blocked 3' ends and suppresses Top1-induced mutagenesis at genomic rNMP sites.Nature structural & molecular biology · 2019Article
- Effect of TDP2 on the Level of TOP2-DNA Complexes and SUMOylated TOP2-DNA Complexes.International journal of molecular sciences · 2018Article
- Fumarase is involved in DNA double-strand break resection through a functional interaction with Sae2.Current genetics · 2018Article
- Physiological functions of programmed DNA breaks in signal-induced transcription.Nature reviews. Molecular cell biology · 2017Review
- Roles of eukaryotic topoisomerases in transcription, replication and genomic stability.Nature reviews. Molecular cell biology · 2016Review
- Clinical and cellular roles for TDP1 and TOP1 in modulating colorectal cancer response to irinotecan.Molecular cancer therapeutics · 2015Article
- Article
- Molecular mechanisms of etoposide.EXCLI journal · 2015Review
- TDP1/TOP1 Ratio as a Promising Indicator for the Response of Small Cell Lung Cancer to Topotecan.Journal of cancer science & therapy · 2014Article
- The N-terminus of Mcm10 is important for interaction with the 9-1-1 clamp and in resistance to DNA damage.Nucleic acids research · 2014Article
- Ultrasensitive isolation, identification and quantification of DNA-protein adducts by ELISA-based RADAR assay.Nucleic acids research · 2014Article
- PARP1-TDP1 coupling for the repair of topoisomerase I-induced DNA damage.Nucleic acids research · 2014Article
- Topoisomerase IIβ deficiency enhances camptothecin-induced apoptosis.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Camptothecin (CPT) and etoposide (ETP) trap topoisomerase-DNA covalent intermediates, resulting in formation of DNA damage that can be cytotoxic if unrepaired. CPT and ETP are prototypes for molecules widely used in chemotherapy of cancer, so defining the mechanisms for repair of damage induced by treatment with these compounds is of great interest. In S. cerevisiae, deficiency in MRE11, which encodes a highly conserved factor, greatly enhances sensitivity to treatment with CPT or ETP. This has been thought to reflect the importance of double-strand break (DSB) repair pathways in the response to these to agents. Here we report that an S. cerevisiae strain expressing the mre11-H59A allele, mutant at a conserved active site histidine, is sensitive to hydroxyurea and also to ionizing radiation, which induces DSBs, but not to CPT or ETP. We show that TDP1, which encodes a tyrosyl-DNA phosphodiesterase activity able to release both 5'- and 3'-covalent topoisomerase-DNA complexes in vitro, contributes to ETP-resistance but not CPT-resistance in the mre11-H59A background. We further show that CPT- and ETP-resistance mediated by MRE11 is independent of SAE2, and thus independent of the coordinated functions of MRE11 and SAE2 in homology-directed repair and removal of Spo11 from DNA ends in meiosis. These results identify a function for MRE11 in the response to topoisomerase poisons that is distinct from its functions in DSB repair or meiotic DNA processing. They also establish that cellular proficiency in repair of DSBs may not correlate with resistance to topoisomerase poisons, a finding with potential implications for stratification of tumors with specific DNA repair deficiencies for treatment with these compounds.
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