Binding to RPA is similar for both p53 (left) and ssDNA (right).

BOCHKAREV/NAS

Single-stranded DNA (ssDNA) and protein can mimic each other, according to Elena Bochkareva, Lilia Kaustov, Cheryl Arrowsmith, Alexey Bochkarev (University of Toronto, Canada), and colleagues. They find structural evidence that ssDNA and a helix from p53 both bind to replication protein A (RPA) in the same position and the same manner—with negative groups poking out and aromatic groups buried in a cleft.

The binding may allow p53 to titrate ssDNA during its response to DNA damage. Before damage, p53 is bound to RPA and thus prevented from acting as a transcriptional activator. When RPA first responds to the ssDNA exposed by DNA damage, it has additional domains that are better specialized for binding ssDNA, so p53 probably comes along for the ride. This exposes p53 to two signals about damage intensity: local...

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