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Using a combination of human B lymphoid leukemia cells and mouse models, we now show that AID expression can be harnessed for antileukemic effect, after inhibition of the RAD51 homologous recombination (HR) factor with 4,4\u2032-diisothiocyanatostilbene-2-2\u2032-disulfonic acid (DIDS). As a proof of principle, we show that DIDS treatment inhibits repair of AID-initiated DNA breaks, induces apoptosis, and promotes cytotoxicity preferentially in AID-expressing human CLL. This reveals a novel antineoplastic role of AID that can be triggered by inhibition of HR, suggesting a potential new paradigm to treat AID-expressing tumors. Given the growing list of tumor types with aberrant AID expression, this novel therapeutic approach has potential to impact a significant patient population.<\/jats:p>","DOI":"10.1084\/jem.20121258","type":"journal-article","created":{"date-parts":[[2013,4,15]],"date-time":"2013-04-15T23:06:55Z","timestamp":1366067215000},"page":"1021-1033","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["Attenuating homologous recombination stimulates an AID-induced antileukemic effect"],"prefix":"10.1084","volume":"210","author":[{"given":"Kristin R.","family":"Lamont","sequence":"first","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneer G.","family":"Hasham","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina M.","family":"Donghia","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Branca","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Chavaree","sequence":"additional","affiliation":[{"name":"CancerCare of Maine, Eastern Maine Medical Center, Brewer, ME 04412 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betsy","family":"Chase","sequence":"additional","affiliation":[{"name":"Maine Center for Cancer Medicine, Scarborough, ME 04074 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Breggia","sequence":"additional","affiliation":[{"name":"Maine Medical Center Research Institute, Scarborough, ME 04074 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn","family":"Hedlund","sequence":"additional","affiliation":[{"name":"Maine Center for Cancer Medicine, Scarborough, ME 04074 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivette","family":"Emery","sequence":"additional","affiliation":[{"name":"Maine Medical Center Research Institute, Scarborough, ME 04074 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cavallo","sequence":"additional","affiliation":[{"name":"Memorial Sloan-Kettering Cancer Center, New York, NY 10065 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Jasin","sequence":"additional","affiliation":[{"name":"Memorial Sloan-Kettering Cancer Center, New York, NY 10065 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"R\u00fcter","sequence":"additional","affiliation":[{"name":"CancerCare of Maine, Eastern Maine Medical Center, Brewer, ME 04412 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Mills","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2013,4,15]]},"reference":[{"key":"2023072601495631600_bib1","doi-asserted-by":"publisher","first-page":"3785","DOI":"10.1200\/JCO.2008.16.0812","article-title":"A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair","volume":"26","author":"Ashworth","year":"2008","journal-title":"J. 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