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Nature cell biology

Cell cycle-specific phase separation regulated by protein charge blockiness

Sidharth Sirdeshmukh

Research Associate, Dewpoint

The general idea is that the patterns of charge differences in proteins will influence the kinetics of their phase separation-guided reassembly. Charge blocks are stretches of amino acids with similar charge, and ‘blockiness’ is the alternation of blocks of opposite charge (+/-). If we make these blocks shorter, then droplet formation is impeded, and droplets that previously existed dissolve/ diffuse. Hyperphosphorylation during mitosis, lengthens the blocks, which encourages droplet formation. Tuning the lengths, the total number, sequence, and likely stochasticity of these kinds of blocks will likely result in favorable LLPS dynamics/ arrangements for diseases with known condensate MOA.