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Is it DNA or protein?

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 kinases and ssDNA itself. The Canadian group shows that ssDNA can compete with p53 for binding to the same site on RPA. Released p53 should be free to activate transcription.

Yet more regulation comes from the phosphorylation of another subunit of RPA. This modified form of RPA is even better than ssDNA at displacing p53 from RPA, although the phosphorylation takes a while to accumulate. A combination of these regulators must somehow communicate the amount of DNA damage to p53 so it can help the cell to choose between apoptosis and the induction of DNA repair.

Reference:

Bochkareva, E., et al. 2005. Proc. Natl. Acad. Sci. USA. 102:15412–15417.[Abstract/Free Full Text]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 799K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?