Loss of Geminin leads to multiple copies of the β-globin gene (red).

Once is enough when it comes to DNA replication—for every cell cycle, chromosomes are replicated just one time to prevent genomic instability. On page 473, Melixetian et al. identify a protein that polices this limitation in human cells.

The replication police officer is Geminin, which prevents replication origins in Xenopus from recruiting licensing proteins that can give the replication go-ahead. In frogs, Geminin does not work alone, as its loss does not induce rereplication. But in human cells, the authors find, Geminin runs the show.

RNAi of Geminin led to additional rounds of replication in both normal and cancerous human cell lines. Rereplication required licensing proteins, suggesting that Geminin works in mammalian cells as it does in frogs.

Rereplicating cells accumulated foci of proteins that bind to double-stranded DNA breaks. The...

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