RFWD3 is a RING-type E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage [, , ].During ICL repair, single-stranded DNA (ssDNA) is generated. The trimeric ssDNA binding protein complex RPA coats the ssDNA. Subsequently, RAD51 is loaded onto RPA-bound ssDNA and catalyzes the critical activity in homologous recombination (HR). RFWD3 polyubiquitinates both RPA and RAD5, which increases their local turnover in DNA damage-induced foci to facilitate HR []. RFWD3-mediated ubiquitination of RPA has been shown to be essential for HR [].
