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Dysfunctional DNA damage response plays an important role in the progression of CKD. We found that BRCA1 expression was increased in the kidneys of patients with CKD and fibrotic kidneys of mice. Exon 11 deletion of Brca1 in proximal tubule cells (PTCs) of mice subjected to ischemic or nephrotoxic (aristolochic acid) injury resulted in a reduced number of senescent cells, as assessed by a decrease in phospho-histone H3, p16INK4a, RAD51 recruitment, G2\/M cell cycle phase cells, GATA4, and senescence-associated \u03b2-galactosidase. There was less production of inflammatory profibrotic mediators and reduced kidney fibrosis. After cisplatin exposure in vitro, human PTCs with reduced BRCA1 had increased apoptosis, decreased RAD51 nuclear foci, and fewer cells in the G2\/M cell cycle phase, with reduced IL-6 and sonic hedgehog production. Thus, BRCA1 regulates nonmalignant tissue responses to kidney injury, a role hitherto unrecognized.<\/jats:p>","DOI":"10.1084\/jem.20231107","type":"journal-article","created":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T02:20:43Z","timestamp":1733538043000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Breast cancer gene-1 (\n                    <i>BRCA1<\/i>\n                    ) potentiates maladaptive repair after kidney injury"],"prefix":"10.1084","volume":"222","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2790-5726","authenticated-orcid":true,"given":"Amrendra K.","family":"Ajay","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wevmz92","id-type":"ROR","asserted-by":"publisher"}],"name":"Brigham and Women\u2019s Hospital, Harvard Medical School 1 Renal Division, Department of Medicine, , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8530-7639","authenticated-orcid":true,"given":"Akinwande A.","family":"Akinfolarin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wevmz92","id-type":"ROR","asserted-by":"publisher"}],"name":"Brigham and Women\u2019s Hospital, Harvard Medical School 1 Renal Division, Department of Medicine, , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4123-0411","authenticated-orcid":true,"given":"Cody C.","family":"Gifford","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wevmz92","id-type":"ROR","asserted-by":"publisher"}],"name":"Brigham and Women\u2019s Hospital, Harvard Medical School 1 Renal Division, Department of Medicine, , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8696-2726","authenticated-orcid":true,"given":"Venkata S.","family":"Sabbisetti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wevmz92","id-type":"ROR","asserted-by":"publisher"}],"name":"Brigham and Women\u2019s Hospital, Harvard Medical School 1 Renal Division, Department of Medicine, , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7144-386X","authenticated-orcid":true,"given":"Joseph V.","family":"Bonventre","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wevmz92","id-type":"ROR","asserted-by":"publisher"}],"name":"Brigham and Women\u2019s Hospital, Harvard Medical School 1 Renal Division, Department of Medicine, , Boston, MA,","place":["USA"]},{"name":"Harvard Stem Cell Institute 2 , Cambridge, MA,","place":["USA"]},{"name":"Harvard-Massachusetts Institute of Technology 3 Division of Health Sciences and Technology, , Cambridge, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"2025032809500012500_bib1","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1681\/ASN.2013020161","article-title":"A bioinformatics approach identifies signal transducer and activator of transcription-3 and checkpoint kinase 1 as upstream regulators of kidney injury molecule-1 after kidney injury","volume":"25","author":"Ajay","year":"2014","journal-title":"J. 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