From S phase to prophase, chromatin must replicate and then condense to prepare for mitosis. In most eukaryotic cells, euchromatin starts the process by replicating first, but it is the last to condense. Heterochromatin is sandwiched in between, opening for replication and then condensing straightaway.
Proper condensation, the authors find, requires Myb, a fly kinase that regulates S phase. Fly cells lacking Myb divided normally for about a dozen cycles but then began to arrest in prophase with condensation errors. “They start to condense,” says Lipsick, “but they can't finish.”
The failure, the group found, lay in euchromatin. Condensation was normal in heterochromatin but failed to spread to euchromatin. Myb was normally found on euchromatin, where it may maintain histone modifications that drive condensation either directly or via other proteins.
Lipsick thinks that cells might use a separate mechanism to make sure that heterochromatin condenses immediately after it replicates. “Heterochromatin is mostly composed of transposons,” he says. “Like a computer virus, its goal is to make more copies of itself. It might be to a cell's advantage to keep it turned off whenever possible.”