XAB2: a link between RNA metabolism, DNA damage repair, and human health

Cells have evolved multiple mechanisms to preserve genome integrity, collectively known as DNA damage response (DDR). Rather than acting separately, the DDR often interacts with transcription and mRNA splicing; however, the underlying molecular mechanisms of this cross-talk are still poorly understood. Consistent with this, components of the splicing machinery are increasingly being recognized as factors with a direct role in sensing, signaling, and repairing DNA damage. Xeroderma pigmentosum group A-binding protein 2 (XAB2), which plays a well-characterized role in mRNA splicing, has also been implicated in the repair of transcription-blocking DNA lesions, transcription elongation, mRNA export, RNA surveillance, and R-loop processing. XAB2 is critical for a wide variety of biological processes, including the mitotic cell cycle, cell differentiation, stress responses, tissue homeostasis, and cellular senescence. However, the mechanism by which XAB2 functions outside of mRNA splicing remains unclear. In this review, we summarize the current knowledge of the biological processes affected by XAB2 in different cellular contexts. Furthermore, we discuss the link between XAB2 and human health, with a particular focus on cancer. This review aims to emphasize the importance of XAB2 and raise awareness of its physiological contributions.