“NUS-AP” deciphers NuSAP function in chromosome

22 Apr 2016 Scientists in NUS have uncovered a novel function of Nucleolar spindle-associated protein (NuSAP) in chromosome segregation.Stability and dynamics of chromosomes are the keys to ensuring proper cell division. During cell division, the dynamics of microtubules are tightly controlled by a number of proteins to ensure the precise alignment of chromosomes at the center of the cell. Impairment of this process leads to chromosome instability, which often causes cells with abnormal numbers of chromosomes (also called aneuploidy) and is a key characteristic of several tumours. However, how chromosome instability induces tumours formation is still a mystery.

A team led by Prof LIOU Yih-Cherng in collaboration with Prof LOW Boon Chuan at the Department of Biological Sciences (DBS) in NUS has uncovered for the first time a novel function of NuSAP in chromosome segregation. NuSAP is a microtubule-associated protein that plays an important role in spindle assembly. Using three-dimensional (3D) live-cell imaging, which allows a general population of the centromeres with 3D information of the oscillation, Prof Liou’s team investigates the role of NuSAP in chromosome orientation, alignment and movement.

Dr LI Chenyu, the first author in the paper, who was a Ph.D. student at DBS, and now a post-doctoral research fellow at Harvard Medical School, discovers that NuSAP is a key regulator for seveal proteins on microtubules and mediates the stability of microtubules; therefore, it plays a critical role in maintaining the normal function of chromsome. This study demonstrates the vital role of NuSAP in controling the complicated regulation of chromosome movement to guard precise chromosome segregation during cell division. In addition to its role in chromsome segregation, Prof Liou’s team also reports in another recent paper² that NuSAP is capable of mediating microtubule dynamics spatially and temporally. Take together, these two papers significantly prove the biophysiological role of NuSAP in ruling chromosome integrity.

Since chromosomal instability is a key characteristic and one of the main causes for many tumours, understanding how NuSAP functions in controlling the precise microtubule dynamics, chromosomal movement, and chromosomal segregation may help to prevent tumour formation and provide a new direction for cancer therapies. It has been reported that NuSAP has abnormal higher levels in many cancers such as pancreatic adenocarcinoma, melanoma, glioma, and hepatocellular, but in the case of colorectal, head and neck, and lymphoma cancer tissues, its level is reduced, suggesting its role in cancers is still an enigma. Moving forward, the team aims to understand the role of NuSAP in chromosomal instability leading to cancer formation.

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Figure shows that a representative 3D time-lapse image of synchronised metaphase mCherry-H2B HeLa cells (upper left), a representative image of 3D centromere tracks colour-coded for time and velocity in monopolar HeLa cells (upper right), a representative 3D time-lapse image of a single chromosome surface of chromosome oscillation in synchronised metaphase mCherry-H2B HeLa cells stably expressing GFP-NuSAP (lower right). A representative image and colour project of microtubule gliding assay with NuSAP and a motor protein (lower left). [Image credit: Liou Yih-Cherng]

References

1. Li C, Xue C, Yang Q, Low BC, Liou YC. “NuSAP governs chromosome oscillation by facilitating the Kid-generated polar ejection force.” Nat Commun. (2016) 7:10597 doi: 10.1038/ncomms10597.

2. Li C, Zhang Y, Yang Q, Ye F, Sun SY, Chen ES, Liou YC. “NuSAP modulates the dynamics of kinetochore microtubules by attenuating MCAK depolymerisation activity.” Sci Rep. (2016) 6:18773. doi: 10.1038/srep18773.