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Methylglyoxal Impairs Sister Chromatid Separation in Lymphocytes. 2022

Leigh Donnellan, and Clifford Young, and Bradley S Simpson, and Varinderpal S Dhillon, and Maurizio Costabile, and Peter Hoffmann, and Michael Fenech, and Permal Deo
Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia.

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.

UI MeSH Term Description Entries
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008277 Magnesium Oxide Magnesium oxide (MgO). An inorganic compound that occurs in nature as the mineral periclase. In aqueous media combines quickly with water to form magnesium hydroxide. It is used as an antacid and mild laxative and has many nonmedicinal uses. Magnesia,Oxide, Magnesium
D011765 Pyruvaldehyde An organic compound used often as a reagent in organic synthesis, as a flavoring agent, and in tanning. It has been demonstrated as an intermediate in the metabolism of acetone and its derivatives in isolated cell preparations, in various culture media, and in vivo in certain animals. Acetylformaldehyde,Methylglyoxal,Oxopropanal,Pyruvic Aldehyde,Aldehyde, Pyruvic
D002842 Chromatids Either of the two longitudinally adjacent threads formed when a eukaryotic chromosome replicates prior to mitosis. The chromatids are held together at the centromere. Sister chromatids are derived from the same chromosome. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Chromatid
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D043171 Chromosomal Instability An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Chromosomal Stability,Chromosome Instability,Chromosome Stability,Chromosomal Instabilities,Chromosomal Stabilities,Chromosome Instabilities,Chromosome Stabilities,Instabilities, Chromosomal,Instabilities, Chromosome,Instability, Chromosomal,Instability, Chromosome,Stabilities, Chromosomal,Stabilities, Chromosome,Stability, Chromosomal,Stability, Chromosome
D018797 Cell Cycle Proteins Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS. Cell Division Cycle Proteins,Cell-Cycle Regulatory Proteins,cdc Proteins,Cell Cycle Regulatory Proteins
D020090 Chromosome Segregation The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS. Chromosome Segregations,Segregation, Chromosome,Segregations, Chromosome

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