Fbh1, or F-box DNA helicase 1, is a member of the UvrD family of DNA helicases [2,5]. It plays a crucial role in the cell's response to replicative stress [2,5]. FBH1 is involved in pathways such as homologous recombination regulation, as it inhibits homologous recombination and catalyzes fork regression when recruited to stalled DNA replication forks by PCNA [2]. It also promotes double-strand break formation and signaling in response to prolonged replication stress, which can initiate apoptosis [3].

FBH1-deficient cells show a reduction in ssDNA and double-strand break signaling when treated with WEE1 inhibitors, indicating its requirement for the induction of replication stress response [1,4]. However, FBH1-deficiency sensitizes cells to WEE1 inhibition by increasing mitotic catastrophe [1,4]. Also, depletion of FBH1 promotes UV-mediated transformation of human melanocytes, suggesting its inactivation contributes to oncogenic transformation [5]. In addition, RAD51 promotes replication stress resistance in FBH1-deficient cells, and depletion of UBC13, which promotes RAD51-dependent template switching, sensitizes FBH1-deficient cells to replication stress, indicating FBH1 regulates template switching to promote replication stress sensitivity [3].

In conclusion, FBH1 is essential for regulating the cell's response to replicative stress, influencing processes like homologous recombination, replication fork handling, and double-strand break signaling. The study of FBH1-deficient models has revealed its significance in cancer-related processes such as oncogenic transformation and response to anti-cancer therapies like WEE1 inhibition, providing insights into potential cancer treatment strategies.