{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T01:20:42Z","timestamp":1788052842396,"version":"build-2784847793"},"reference-count":65,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Letters"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:p>tRNA methyltransferase 9 (Trm9)\u2010catalysed tRNA modifications have been shown to translationally enhance the DNA damage response (DDR). Here, we show that <jats:italic>Saccharomyces cerevisiae trm9<\/jats:italic>\u0394, distinct DNA repair and spindle assembly checkpoint (SAC) mutants are differentially sensitive to the aminoglycosides tobramycin, gentamicin and amikacin, indicating DDR and SAC activation might rely on translation fidelity, under aminoglycoside stress. Further, we report that the DNA damage induced by aminoglycosides in the base excision repair mutants <jats:italic>ogg1<\/jats:italic>\u0394 and <jats:italic>apn1<\/jats:italic>\u0394 is mediated by reactive oxygen species, which induce the DNA adduct 8\u2010hydroxy deoxyguanosine. Finally, the synergistic effect of tobramycin and the DNA\u2010damaging agent bleomycin to sensitize <jats:italic>trm9<\/jats:italic>\u0394 and the DDR mutants <jats:italic>mlh1<\/jats:italic>\u0394, <jats:italic>rad51<\/jats:italic>\u0394, <jats:italic>mre11<\/jats:italic>\u0394 and <jats:italic>sgs1<\/jats:italic>\u0394 at significantly lower concentrations compared with wild\u2010type suggests that cells with tRNA modification dysregulation and DNA repair gene defects can be selectively sensitized using a combination of translation inhibitors and DNA\u2010damaging agents.<\/jats:p>","DOI":"10.1002\/1873-3468.14591","type":"journal-article","created":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T07:54:49Z","timestamp":1674892489000},"page":"1149-1163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Loss of <scp>tRNA<\/scp> methyltransferase 9 and <scp>DNA<\/scp> damage response genes in yeast confers sensitivity to aminoglycosides"],"prefix":"10.1002","volume":"597","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9958-7355","authenticated-orcid":false,"given":"Bhavana","family":"Veerabhadrappa","sequence":"first","affiliation":[{"name":"Department of Biotechnology R V College of Engineering \u2010 Visvesvaraya Technological University  Bengaluru Karnataka India"},{"name":"Department of Biochemistry and Molecular Biology, School of Life Sciences Pondicherry University  Pondicherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1278-7069","authenticated-orcid":false,"given":"Sudharshan","family":"SJ","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Life Sciences Pondicherry University  Pondicherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagashree N.","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Biotechnology R V College of Engineering \u2010 Visvesvaraya Technological University  Bengaluru Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7804-9048","authenticated-orcid":false,"given":"Madhu","family":"Dyavaiah","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Life Sciences Pondicherry University  Pondicherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a027029"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13737"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1715501114"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.805208"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms16010321"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.24.9283-9292.2003"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.09.021"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157611"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2858"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0300-x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2012.12.003"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157611"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsle\/fnab077"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/1567-1364.12202"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsle\/fnz065"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fob.2014.01.002"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.07.005"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-11-92"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.09.059"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2018-0404"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx400438d"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2014.01.008"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201201161"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.4161\/rna.20531"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005150"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004678"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx700283c"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi048276x"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.11.024"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.10.022"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1715501114"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1715578115"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04972.x"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2012.09.008"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.09.038"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20039"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2015.4"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004639"},{"key":"e_1_2_10_40_1","first-page":"845","article-title":"Base excision repair targets for cancer therapy","volume":"1","author":"Dianov GL","year":"2011","journal-title":"Am J Cancer Res"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.06.012"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05269"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.04.020"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0131335"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv222"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh165"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2018.04.004"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001024"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001247"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-76426-2"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn302"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(78)80016-5"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-251"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060614-033923"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2017.04.006"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.22953"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0243-7"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2007.115"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/narcan\/zcab016"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/narcan\/zcaa024"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.2.283"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210880"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1355"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2014.00366"}],"container-title":["FEBS Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1873-3468.14591","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/1873-3468.14591","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1873-3468.14591","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T20:44:53Z","timestamp":1692650693000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/1873-3468.14591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,7]]},"references-count":65,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/1873-3468.14591"],"URL":"https:\/\/doi.org\/10.1002\/1873-3468.14591","archive":["Portico"],"relation":{},"ISSN":["0014-5793","1873-3468"],"issn-type":[{"value":"0014-5793","type":"print"},{"value":"1873-3468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,7]]},"assertion":[{"value":"2022-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}