Methylglyoxal Impairs Sister Chromatid Separation in Lymphocytes

Abstract

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.

An Introduction to the Special Issue “Protein Glycation in Food, Nutrition, Health and Disease”

“…Glo1, which suppresses levels of MG and MGdG, is also a tumor suppressor protein [ 9 , 26 ]. In this Special Issue, Donnellan et al [ 27 ] describe how high levels of exogenous MG impair sister chromatid separation in lymphocytes, which may be related to the tumorigenesis activity of MG and is consistent with the tumor suppressor activity of Glo1 [ 26 ]. Glo1 inhibitors have been developed for cancer chemotherapy to induce an increase in cellular MG for cytotoxic effects.…”