Plant PAXX has an XLF-like function and stimulates DNA end joining by the Ku-DNA ligase IV/XRCC4 complex

Non-homologous end joining (NHEJ) plays a major role in repairing DNA double-strand breaks and is key to genome stability and editing. The minimal core NHEJ proteins, namely Ku70, Ku80, DNA ligase IV and XRCC4, are conserved, but other factors vary in different eukaryote groups. In plants, the only known NHEJ proteins are the core factors, while the molecular mechanism of plant NHEJ remains unclear. Here, we report a previously unidentified plant ortholog of PAXX, the crystal structure of which showed a similar fold to human 'PAXX'. However, plant PAXX has similar molecular functions to human XLF, by directly interacting with Ku70/80 and XRCC4. This suggests that plant PAXX combines the roles of mammalian PAXX and XLF and that these functions merged into a single protein during evolution. This is consistent with a redundant function of PAXX and XLF in mammals.

Automated summary

Non-homologous end joining (NHEJ) is important for repairing DNA double-strand breaks in plants, but the molecular mechanism of plant NHEJ is still unclear. This study discovered a previously unidentified plant ortholog of PAXX, which has a similar structure to human PAXX but functions similar to human XLF by interacting with Ku70/80 and XRCC4. This suggests that plant PAXX combines the roles of mammalian PAXX and XLF, indicating a functional redundancy between PAXX and XLF in plants.