NuSAP Protein Safeguards Centriole Structure During Cell Division

Biologists at the National University of Singapore (NUS) have uncovered how the protein NuSAP safeguards tiny structures inside cells called centrioles, revealing a mechanism linked to developmental disorders such as microcephaly and mosaic variegated aneuploidy (MVA) syndrome.

Cells rely on tight control of the centrosome, a small "control centre" that helps organise cell division, to make sure each new cell receives the correct set of genetic instructions during division. If centrosome regulation is disrupted, the cell can form abnormal division structures and mishandle chromosomes, leading to errors that may contribute to developmental problems or disease.

A research team led by Associate Professor LIOU Yih-Cherng from the NUS Department of Biological Sciences found that the microtubule-associated protein NuSAP plays a critical role in stabilising centriole architecture and coordinating the recruitment of proteins necessary for proper centrosome engagement.

The findings were published in the journal Advanced Science on 30 January 2026. 

Dr. Zhang Shiyu, a Research Fellow at the NUS Department of Biological Sciences, said, "Accurate cell division is fundamental to human development. Our study shows that the protein NuSAP acts as a guardian of centrosome integrity. When this protection fails, chromosome errors can accumulate, a hallmark of disorders such as microcephaly and MVA syndrome."

Why Centriole Integrity Matters

Each time a cell divides, it must faithfully duplicate and distribute its genetic material. This process depends on centrosomes, which organise microtubules and form the mitotic spindle. At the core of each centrosome are two centrioles that must remain tightly "engaged" after duplication and only separate at the correct stage of the cell cycle.

If this coordination fails, cells can develop abnormal centrosome numbers, chromosome mis-segregation, and genomic instability, leading to defects associated with developmental disorders and cancer. However, how centriole structural integrity is preserved has remained incompletely understood.

A Newly Identified Structural Safeguard

The research team discovered that NuSAP, previously recognized for its role in spindle organisation during mitosis, also functions earlier in the cell cycle to protect centriole structure. Using super-resolution imaging and biochemical approaches, they found that loss of NuSAP damages the centriole's internal scaffold, disrupts the surrounding support material, and causes the centriole pair to separate too early.

Importantly, NuSAP was shown to be required to bring in a key "ring" of helper proteins (CEP57–CEP63–CEP152 torus complex) that wraps around the centriole and helps keep the two centrioles attached until the right time. The study also showed that NuSAP physically binds to one of these helper proteins, called CEP57, and helps position it early on, just before the cell enters division.