CtIP Regulates Mitotic Spindle Assembly by Modulating the TPX2-Aurora A Signaling Axis

Abstract

CtBP-interacting protein (CtIP) plays a critical role in controlling the homologous recombination-mediated DNA double-stranded break (DSB) repair pathway through DNA end resection, and recent studies suggest that it also plays a role in mitosis. However, the mechanism by which CtIP contributes to mitosis regulation remains elusive. Here, we show that depletion of CtIP leads to a delay in anaphase progression resulting in misaligned chromosomes, an aberrant number of centrosomes, and defects in chromosome segregation. Additionally, we demonstrate that CtIP binds and colocalizes with Targeting protein for Xklp2 (TPX2) during mitosis to regulate the recruitment of TPX2 to the spindle poles. Furthermore, depletion of CtIP resulted in both a lower concentration of Aurora A, its downstream target, and very low microtubule intensity at the spindle poles, suggesting an important role for the CtIP-TPX2-Auroa A complex in microtubule dynamics at the centrosomal spindles. Our findings reveal a novel function of CtIP in regulating spindle dynamics through interactions with TPX2 and indicate that CtIP is involved in the proper execution of the mitotic program, where deregulation may lead to chromosomal instability.

Keywords

• CtIP
• spindle
• mitosis
• TPX2
• kinetochore
• spindle assembly checkpoint