WDR70 is a WD repeat domain protein that functions as a substrate recognition subunit of the CRL4 (Cullin4-DDB1-RING) ubiquitin ligase complex, specifically forming CRL4^WDR70 1. The primary function of WDR70 is to facilitate DNA double-strand break repair through homologous recombination by promoting H2B monoubiquitination at lysine 119/120 at DNA damage sites 12. Mechanistically, WDR70 is recruited to double-strand breaks where CRL4^WDR70 stimulates distal H2B monoubiquitination, which prevents loading of the resection inhibitor Crb2/53BP1 and facilitates Exo1-dependent DNA end resection 1. WDR70 also plays a role in mRNA processing, as it regulates nuclear retention of intron-containing mRNAs, including HIV-1 transcripts 3. Disease relevance includes frequent mutations in ovarian cancer specimens that disrupt homologous recombination and cause chr5 instability 45. The hepatitis B virus X protein targets WDR70 to inhibit H2B monoubiquitination, leading to impaired DNA repair and contributing to hepatocarcinogenesis 2. WDR70 expression is also dysregulated in prostate cancer 6 and is associated with 5p13 microduplication syndrome 7.