AsianScientist (Feb. 7, 2018) – In a study published in Current Biology, Japanese researchers have invented an ion detector and used it to demonstrate the importance of magnesium ions (Mg2+) in the folding of DNA into chromosomes.
Cell division is essential for new cells to form in the body, be it during normal growth or to repair lost or damaged cells. During cell division, chromosomes begin to condense and remain so until the division is complete. A number of proteins in the cell control the condensation, but so too do free ions such as Mg2+. However, quantitatively measuring magnesium ion concentration during cell division has been a challenge.
In the present study, a team of researchers led by Professor Kazuhiro Maeshima at the National Institute of Genetics in Osaka University, Japan, developed a chemical probe that can be used to detect intracellular signaling. Called MARIO (Magnesium Ratiometric Indicator for Optical Imaging), the fluorescent probe measures Mg2+ concentrations in living cells.
MARIO is based on a calcium indicator known as YC3.60 and is composed of enhanced cyan fluorescent protein, the yellow fluorescent protein VENUS, and a Mg2+-binding domain found in bacteria known as CorA. Mg2+ binding to CorA causes a structural change in MARIO that changes the fluorescence signal.
“We could improve MARIO’s performance, both in terms of Mg2+ affinity and dynamic range, by truncating CorA and by introducing random mutations into the structure,” said Professor Takeharu Nagai of Osaka University, who is a co-author of the study.
Mg2+ itself is abundant in the cell, but not in the free form. Instead it is usually captured by ATP. Using MARIO, the researchers found that during cell division, free Mg2+ greatly increases, enabling the chromosomes to condense. The increase peaked during the transition from metaphase to anaphase, which marks the period in cell division when the cell membrane begins to show signs of pinching off to form two cells.
“We found a clear relationship between ATP levels and free Mg2+,” said Maeshima. “The less ATP there was, the more Mg2+ became freely available, and this corresponded with more chromosome condensation. We propose a novel mechanism of regulation during cell division, in which ATP-bound Mg2+ is released by the hydrolysis of ATP.”
“A number of diseases like cancer are caused by abnormalities in cell division. We expect that insights into the regulation of chromosome condensation will help us understand how these diseases develop, as well as help us develop and possible ways to treat them,” he added.
Source: Osaka University; Photo: Shutterstock.
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