In a groundbreaking study published in the journal Advanced Science, researchers at the National University of Singapore (NUS) have elucidated a critical mechanism by which cells maintain the structural integrity of centrioles—microscopic cylindrical organelles fundamental for accurate cell division. At the heart of this discovery is the microtubule-associated protein NuSAP, which acts as a “guardian” to ensure the proper assembly and engagement of centrioles, thereby safeguarding the fidelity of genetic material during cell division. This advance provides important new insights into the origins of developmental disorders like microcephaly and mosaic variegated aneuploidy (MVA) syndrome, conditions associated with chromosome instability.
Centrioles serve as the core components of centrosomes, the principal microtubule-organizing centers responsible for orchestrating the assembly of the mitotic spindle apparatus during mitosis. These cylindrical structures exist as tightly linked pairs that must maintain precise engagement following duplication to guarantee the accurate segregation of chromosomes. Disruption of centriole cohesion or premature disengagement can provoke centrosome amplification, erroneous spindle formation, and ensuing chromosomal missegregation—hallmarks of developmental defects and tumorigenesis. Yet, until now, the molecular safeguards that preserve centriole structural integrity throughout the cell cycle remained incompletely characterized.
The investigative team led by Associate Professor LIOU Yih-Cherng utilized sophisticated super-resolution microscopy and biochemical assays to unveil the pivotal role of NuSAP beyond its established function in spindle microtubule stabilization. Remarkably, NuSAP operates earlier in the cell cycle to fortify the centriole’s internal scaffold and maintain the organization of pericentriolar material (PCM), a proteinaceous matrix that provides structural support and recruits essential centrosomal proteins. Loss of NuSAP induces destabilization of the centriolar tubulin framework and disarray of the PCM architecture, resulting in aberrant centriole separation and compromised centrosome functionality.
Central to the study’s findings is the demonstration that NuSAP dynamically recruits and positions a crucial protein complex, the CEP57–CEP63–CEP152 “torus,” which encircles the centriole and mediates the physical tethering between mother and procentriole units. This complex ensures the centrioles remain properly engaged during the S to G2 phases of the cell cycle, a prerequisite for subsequent orderly chromosome segregation. NuSAP was shown to bind directly to CEP57, facilitating its timely localization and stabilizing the torus structure. In the absence of NuSAP, inefficient recruitment of this complex leads to premature centriole disengagement, disrupting the delicate coordination necessary for centrosome function.
This two-step recruitment model proposes that during DNA synthesis through G2 phase, NuSAP-dependent CEP57 localization acts as an anchoring point assembling the CEP57-CEP63-CEP152 complex around the procentriole. The ensuing toroidal formation fosters precise centriole engagement and robust PCM organization. Conversely, NuSAP deficiency compromises tubulin stability, weakening centriole integrity and perturbing this recruitment cascade, which culminates in centrosomal disarray. This mechanistic insight fills a vital gap in understanding how centriole architecture is preserved through rigorous temporal and spatial control within cycling cells.
From a developmental biology perspective, the study’s implications are profound. Precise chromosome segregation is indispensable for embryonic development, and defects in centrosome regulation often manifest as diseases characterized by impaired neurodevelopment, notably microcephaly, where reduced brain size correlates with abnormal neural progenitor proliferation. The researchers posit that NuSAP malfunction could underlie such pathologies by enabling chromosome missegregation during early cell divisions. Furthermore, genomic instability from centrosome defects has long been linked to cancer progression, suggesting NuSAP’s protective role may extend to tumor suppression.
Technically, the research combined molecular genetic tools and advanced imaging techniques—such as STED and 3D structured illumination microscopy—to visualize centriole architecture at unprecedented resolution. Protein–protein interactions were delineated using co-immunoprecipitation assays, confirming NuSAP’s direct binding to CEP57. Additionally, live-cell imaging tracked centriole dynamics under NuSAP perturbation, revealing the temporal sequence of aberrations culminating in centriole disengagement. This comprehensive methodological approach underscores the robustness of the findings.
Historically, NuSAP was appreciated primarily for its role in organizing spindle microtubules during mitosis, stabilizing their attachment to kinetochores and aiding chromosome congression. This study extends NuSAP’s functional repertoire by defining its early cell cycle activity crucial for structural scaffolding of the centriole complex. Such dual functionality exemplifies the multifaceted regulation of centrosomal proteins, reflecting the intricate ballet of molecular events safeguarding genomic integrity.
Looking forward, the study opens avenues for targeted therapeutic interventions addressing diseases linked to centrosome dysfunction. Modulating NuSAP activity or enhancing the stability of the CEP57–CEP63–CEP152 complex could restore centriole engagement fidelity and prevent chromosomal instability. Moreover, further research into the molecular determinants governing NuSAP’s interaction network will illuminate additional layers of centrosome regulation.
In summary, the NUS team’s discovery of NuSAP’s role as a “centriole bodyguard” advances our comprehension of cellular division machinery by revealing how centriole structural integrity is meticulously preserved. Their identification of NuSAP-mediated recruitment of the CEP57–CEP63–CEP152 torus complex underscores a critical checkpoint in centrosome biology, illuminating molecular pathways that maintain genomic stability and prevent developmental disorders. As the cornerstone of chromosomal fidelity during cell division, centrioles demand such precise safeguards—now better understood thanks to these pivotal findings.
Subject of Research: Cells
Article Title: NuSAP Safeguards Centriole Integrity to Mediate CEP57–CEP152 Torus Recruitment for Proper Engagement
News Publication Date: 30-Jan-2026
Web References:
10.1002/advs.202515192
Image Credits: Created in BioRender. Liou Y. (2026)
Keywords: Cell biology, Centrioles, Centrosome integrity, NuSAP protein, CEP57–CEP63–CEP152 complex, Mitosis, Chromosome segregation, Microtubule-associated proteins, Microcephaly, Genomic instability
