Htatsf1, also known as HIV Tat-specific factor 1, is an RNA-binding protein involved in multiple biological processes. It plays a crucial role in homologous recombination (HR), a DNA double-strand break repair mechanism closely related to genome stability and tumor response to chemotherapy [1,2]. It also participates in regulating embryonic stem cell differentiation by controlling various aspects of RNA processing during ribosome biogenesis [3].

In HR, CK2 phosphorylates Htatsf1 to promote its binding to TOPBP1, facilitating S-phase-specific TOPBP1 recruitment to damaged chromatin and subsequent RPA/RAD51-dependent HR [1]. In tumors, the CK2-Htatsf1-TOPBP1 axis is often hyperactivated, rendering breast tumors less responsive to chemotherapy. Deletion mutations of Htatsf1 in breast and lung tumor samples predict higher HR deficiency scores, and tumor cells with Htatsf1 loss-of-function mutations are vulnerable to poly(ADP-ribose) polymerase inhibitors or platinum drugs [2]. In embryonic stem cells, Htatsf1, in complex with SF3B1, controls intron removal from ribosomal protein transcripts and ribosomal RNA transcription and processing, thus regulating 60S ribosomal abundance and protein synthesis, which is essential for early mammalian embryogenesis [3].

In summary, Htatsf1 is essential for DNA repair through its role in homologous recombination and for embryonic stem cell differentiation via its influence on ribosome biogenesis. The study of Htatsf1 knockout or conditional knockout mouse models has revealed its significance in tumorigenesis and chemotherapy response, providing insights into potential therapeutic strategies for cancer treatment.