When the RAP (80) fades out, you can hear BRCA1 RING

The tumor suppressor protein BRCA1 plays an important role in DNA repair by homologous recombination. Despite being encoded by the first familial breast and ovarian cancer gene identified, how BRCA1 is recruited to sites of DNA damage to execute its repair functions has remained poorly understood. Several recent studies highlight the role of its constitutive interaction partner BARD1 in this process. In this issue, parallel work by Sherker et al (2021) focused on a second route of BRCA1 recruitment, connected to the BRCA1-A complex protein RAP80. Studying BRCA1 recruitment in RAP80-deficient cells exposed a critical role for the BRCA1 RING domain and its associated ubiquitin ligase activity. Given that tumors expressing RING-less BRCA1 isoforms can become resistant to therapy, targeting the RAP80 recruitment axis in such tumors might restore effective treatment.