Methylglyoxal Impairs Sister Chromatid Separation in Lymphocytes

International Journal of Molecular Sciences

Clifford Young¹  Peter Hoffmann¹  Leigh Donnellan²  Maurizio Costabile²  Bradley S. Simpson²  Varinderpal S. Dhillon²  Michael Fenech²  Permal Deo² 

[1]Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia

[2]Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia

关键词: methylglyoxal;    chromosomal instability;    sister chromatid separation;    proteomics;   

DOI  :  10.3390/ijms23084139

来源: DOAJ

【 摘 要 】

The accurate segregation of sister chromatids is complex, and errors that arise throughout this process can drive chromosomal instability and tumorigenesis. We recently showed that methylglyoxal (MGO), a glycolytic by-product, can cause chromosome missegregation events in lymphocytes. However, the underlying mechanisms of this were not explored. Therefore, in this study, we utilised shotgun proteomics to identify MGO-modified proteins, and label-free quantitation to measure changes in protein abundance following exposure to MGO. We identified numerous mitotic proteins that were modified by MGO, including those involved in the separation and cohesion of sister chromatids. Furthermore, the protein abundance of Securin, an inhibitor of sister chromatid separation, was increased following treatment with MGO. Cytological examination of chromosome spreads showed MGO prevented sister chromatid separation, which was associated with the formation of complex nuclear anomalies. Therefore, results from this study suggest MGO may drive chromosomal instability by preventing sister chromatid separation.

【 授权许可】

Unknown