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Adv."],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:p>\n                    Rhabdoid tumors (RTs) are highly aggressive cancers driven by biallelic mutation of\n                    <jats:italic toggle=\"yes\">SMARCB1<\/jats:italic>\n                    , a core subunit of the BAF (SWI\/SNF) complex. We found that\n                    <jats:italic toggle=\"yes\">SMARCB1<\/jats:italic>\n                    -deficient tumors have a defect in the microhomology-mediated end joining (MMEJ) pathway, and SMARCB1 is essential for maintaining the protein level of the core MMEJ protein, DNA Polymerase theta (Pol\u0398). Mechanistically, SMARCB1 facilitates the nuclear export of the\n                    <jats:italic toggle=\"yes\">POLQ<\/jats:italic>\n                    mRNA through its interaction with the nuclear pore complex. Interestingly, loss of MMEJ in RT cells leads to a compensatory activation of, and a hyper-dependence on, the Fanconi Anemia (FA)\/BRCA pathway. Notably, degraders of RBM39, a splicing modulator, show strong antitumor efficacy in RT models in vitro and in vivo by disrupting FA\/BRCA pathway. SMARCB1 and other cBAF\/pBAF components are important for maintenance of MMEJ activity and Pol\u0398 protein level, suggesting that BAF-deficient cancers more broadly may be treated by targeted inhibition of the FA\/BRCA pathway.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aed7743","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T17:58:41Z","timestamp":1786730321000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Defective microhomology-mediated end joining in\n                    <i>SMARCB1<\/i>\n                    -deficient tumors"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5895-1349","authenticated-orcid":true,"given":"Guangli","family":"Zhu","sequence":"first","affiliation":[{"name":"Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 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