Crumbs interacts with Xpd for nuclear division control in Drosophila

Crumbs (Crb) family proteins are crucial for cell polarity. Recent studies indicate that they are also involved in growth regulation and cancer. However, it is not well-understood how Crb participates in mitotic processes. Here, we report that Drosophila Crb is critically involved in nuclear division by interacting with Xeroderma pigmentosum D (XPD). A novel gene named galla-1 was identified from a genetic screen for crb modifiers. Galla-1 protein shows homology to MIP18, a subunit of the mitotic spindle-associated MMS19-XPD complex. Loss-of-function galla-1 mutants show abnormal chromosome segregation, defective centrosome positions and branched spindles during nuclear division in early embryos. Embryos with loss-of-function or overexpression of crb show similar mitotic defects and genetic interaction with galla-1. Both Galla-1 and Crb proteins show overlapping localization with spindle microtubules during nuclear division. Galla-1 physically interacts with the intracellular domain of Crb. Interestingly, Galla-1 shows little binding to the Drosophila homolog of XPD, but a related protein Galla-2 binds both Crb and Xpd. Loss-of-function galla-2 mutants show similar mitotic defects as galla-1 and strong genetic interaction with crb. Xpd can form a physical complex with Crb. In imaginal disc, Crb overexpression causes tissue overgrowth as well as DNA damages marked by H2Av phosphorylation. These phenotypes are suppressed by reduction of Xpd. Taken together, this study identifies a novel Crb-Galla-Xpd complex and its function for proper chromosome segregation during nuclear division, implicating a potential link between Crb and Xpd-related genome instability.