{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:05:18Z","timestamp":1789452318225,"version":"build-2803163510"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Parasitol."],"abstract":"<jats:p>\n                    The RecQ helicase PfBlm from the human malaria parasite\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    plays a critical role in maintaining genome integrity through its function in homologous recombination mediated DNA repair. Given its essential role in resolving recombination intermediates, PfBlm has emerged as a potential antimalarial drug target. Chemical inhibition of PfBlm helicase activity using the small-molecule inhibitor ML216 sensitize the parasites towards DNA damage inducing agents. Here, we investigated whether inhibition of the molecular chaperone PfHsp90 enhances the antimalarial efficacy of ML216. We demonstrate that the co-treatment with 17-AAG resulted in a marked reduction in the IC\n                    <jats:sub>50<\/jats:sub>\n                    of ML216, indicating potentiation of PfBlm inhibition upon PfHsp90 targeting. We report that PfHsp90 functionally associates with PfBlm and promotes UV irradiation\u2013induced DNA repair by regulating PfBlm stability. Combined inhibition of PfHsp90 and PfBlm caused a pronounced and sustained defect in DNA repair that exceeded the effects of each of the individual inhibitors, consistent with a functional interaction. Together, these findings suggest that PfHsp90 contributes to PfBlm stability and activity, thus provide a rationale for simultaneously targeting PfHsp90 and PfBlm as a strategy to block parasite DNA repair and limit parasite survival.\n                  <\/jats:p>","DOI":"10.3389\/fpara.2026.1896831","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:36:04Z","timestamp":1789450564000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of Plasmodium DNA double strand repair by the combined action of 17-AAG and ML216"],"prefix":"10.3389","volume":"5","author":[{"given":"Km","family":"Tanishka","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Life Sciences, University of Hyderabad","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wahida","family":"Tabassum","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Life Sciences, University of Hyderabad","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak Kumar","family":"Rout","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Life Sciences, University of Hyderabad","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Life Sciences, University of Hyderabad","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mrinal Kanti","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Life Sciences, University of Hyderabad","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103819","article-title":"Association of BLM and BRCA1 during telomere maintenance in ALT cells","volume":"9","author":"Acharya","year":"2014","journal-title":"PloS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/0166-6851(93)90069-a","article-title":"Origin of reactive oxygen species in erythrocytes infected with Plasmodium falciparum","volume":"61","author":"Atamna","year":"1993","journal-title":"Mol. Biochem. Parasitol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s00412-007-0142-4","article-title":"RecQ helicases: Guardian angels of the DNA replication fork","volume":"117","author":"Bachrati","year":"2008","journal-title":"Chromosoma"},{"key":"B4","doi-asserted-by":"publisher","first-page":"18336","DOI":"10.1074\/jbc.m211309200","article-title":"Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytes","volume":"278","author":"Banumathy","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1016\/s0020-7519(03)00212-1","article-title":"Identification and molecular characterisation of DNA damaging agent induced expression of Plasmodium falciparum recombination protein PfRad51","volume":"33","author":"Bhattacharyya","year":"2003","journal-title":"Int. J. Parasitol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.molbiopara.2004.09.007","article-title":"Characterization of kinetics of DNA strand-exchange and ATP hydrolysis activities of recombinant PfRad51, a Plasmodium falciparum recombinase","volume":"139","author":"Bhattacharyya","year":"2005","journal-title":"Mol. Biochem. Parasitol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"14966","DOI":"10.1074\/jbc.m900195200","article-title":"Telomerase-associated protein 1, HSP90, and topoisomerase II\u03b1 associate directly with the BLM helicase in immortalized cells using ALT and modulate its helicase activity using telomeric DNA substrates","volume":"284","author":"Bhattacharyya","year":"2009","journal-title":"J. Biol. 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