RNF19A-mediated ubiquitination of BARD1 prevents BRCA1/BARD1-dependent homologous recombination

• DOI: 10.1038/s41467-021-27048-3
• Publication Date: 2021-11-17T11:03:51Z
• Authors: Qian Zhu; Jinzhou Huang; Hongyang Huang; Huan Li; Peiqiang Yi; Jake A. Kloeber; Jian Yuan; Yuping Chen; Min Deng; Kuntian Luo; Ming Gao; Guijie Guo; Xinyi Tu; Ping Yin; Yong Zhang; Jun Su; Jiayi Chen; Zhenkun Lou
• Keywords: Nuclear export signal

Abstract BRCA1-BARD1 heterodimers act in multiple steps during homologous recombination (HR) to ensure the prompt repair of DNA double strand breaks. Dysfunction BRCA1 pathway enhances therapeutic efficiency poly-(ADP-ribose) polymerase inhibitors (PARPi) cancers, but molecular mechanisms underlying this sensitization PARPi are not fully understood. Here, we show that cancer cell sensitivity is promoted by ring between fingers (RBR) protein RNF19A. We demonstrate RNF19A suppresses HR ubiquitinating BARD1, which leads dissociation complex and exposure a nuclear export sequence BARD1 otherwise masked BRCA1, resulting cytoplasm. provide evidence high expression breast compromises increases PARPi. propose modulates response negatively regulating inhibiting HR-mediated repair.