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

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 mi...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2022-09, Vol.11 (18), p.2814
Main Authors: Oh, Wonkyung, Wu, Ting Ting, Jeong, Seo-Yeon, You, Ho Jin, Lee, Jung-Hee
Format: Article
Language:English
Subjects:
Anaphase
Antibodies
Biotechnology
Cell cycle
Cell division
Centrosomes
Chromosomes
CtIP
DNA damage
DNA repair
Double-strand break repair
Genomic instability
Homologous recombination
Kinases
kinetochore
Laboratories
Microscopy
Mitosis
Plasmids
Proteins
spindle
spindle assembly checkpoint
Spindles
TPX2
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Summary: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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells11182814