A Transient Rise in Free Mg2+ Ions Released from ATP-Mg Hydrolysis Contributes to Mitotic Chromosome Condensation

Kazuhiro Maeshima, Tomoki Matsuda, Yutaka Shindo, Hiromi Imamura, Sachiko Tamura, Ryosuke Imai, Syoji Kawakami, Ryosuke Nagashima, Tomoyoshi Soga, Hiroyuki Noji, Kotaro Oka, Takeharu Nagai

Research output: Contribution to journalArticlepeer-review

94 Citations (Scopus)


For cell division, negatively charged chromatin, in which nucleosome fibers (10 nm fibers) are irregularly folded [1–5], must be condensed into chromosomes and segregated. While condensin and other proteins are critical for organizing chromatin into the appropriate chromosome shape [6–17], free divalent cations such as Mg2+ and Ca2+, which condense chromatin or chromosomes in vitro [18–28], have long been considered important, especially for local condensation, because the nucleosome fiber has a net negative charge and is by itself stretched like “beads on a string” by electrostatic repulsion. For further folding, other positively charged factors are required to decrease the charge and repulsion [29]. However, technical limitations to measure intracellular free divalent cations, but not total cations [30], especially Mg2+, have prevented us from elucidating their function. Here, we developed a Förster resonance energy transfer (FRET)-based Mg2+ indicator that monitors free Mg2+ dynamics throughout the cell cycle. By combining this indicator with Ca2+ [31] and adenosine triphosphate (ATP) [32] indicators, we demonstrate that the levels of free Mg2+, but not Ca2+, increase during mitosis. The Mg2+ increase is coupled with a decrease in ATP, which is normally bound to Mg2+ in the cell [33]. ATP inhibited Mg2+-dependent chromatin condensation in vitro. Chelating Mg2+ induced mitotic cell arrest and chromosome decondensation, while ATP reduction had the opposite effect. Our results suggest that ATP-bound Mg2+ is released by ATP hydrolysis and contributes to mitotic chromosome condensation with increased rigidity, suggesting a novel regulatory mechanism for higher-order chromatin organization by the intracellular Mg2+-ATP balance. How the negatively charged long genomic DNA is organized into mitotic chromosome remains unclear. Using a newly developed Mg2+ indicator, Maeshima et al. demonstrate a transient rise in free Mg2+ released from ATP-Mg during mitosis and suggest that the rise contributes to mitotic chromosome condensation by charge neutralization.

Original languageEnglish
Pages (from-to)444-451.e6
JournalCurrent Biology
Issue number3
Publication statusPublished - 2018 Feb 5


  • ATP
  • Ca
  • FRET
  • Mg
  • chromosome condensation
  • condensin
  • indicator
  • live-cell imaging
  • mitotic chromosome
  • nucleosome

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


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