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Both CSC and chemoresistant cancer cells may share common qualities to activate a series of self\u2010defense mechanisms against chemotherapeutic drugs. Here, we aimed to identify proteins in chemoresistant triple\u2010negative breast cancer (TNBC) cells and corresponding CSC\u2010like spheroid cells that may contribute to their resistance. We have identified several candidate proteins representing the subfamilies of DNA damage response (DDR) system, the ATP\u2010binding cassette, and the 26S proteasome degradation machinery. We have also demonstrated that both cell types exhibit enhanced DDR when compared to corresponding parental counterparts, and identified RAD50 as one of the major contributors in the resistance phenotype. Finally, we have provided evidence that depleting or blocking RAD50 within the Mre11\u2013Rad50\u2013NBS1 (MRN) complex resensitizes CSC and chemoresistant TNBC cells to chemotherapeutic drugs.<\/jats:p>","DOI":"10.1111\/febs.15588","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T04:23:09Z","timestamp":1602217389000},"page":"2184-2202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Enhanced DNA damage response through RAD50 in triple negative breast cancer resistant and cancer stem\u2010like cells contributes to chemoresistance"],"prefix":"10.1111","volume":"288","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9431-5817","authenticated-orcid":false,"given":"Etna","family":"Abad","sequence":"first","affiliation":[{"name":"Vall d'Hebron Research Institute (VHIR) Barcelona Spain"},{"name":"Department of Experimental and Health Sciences Universitat Pompeu Fabra Barcelona 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