DOI: 10.1073/pnas.0504614102. Single-stranded DNA mimicry in the p53 transactivation domain interaction with replication protein A

Single-stranded DNA mimicry in the p53 transactivation domain interaction with replication protein A

10.1073/pnas.0504614102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

One of many protein–protein interactions modulated upon DNA damage is that of the single-stranded DNA-binding protein, replication protein A (RPA), with the p53 tumor suppressor. Here we report the crystal structure of RPA residues 1–120 (RPA70N) bound to the N-terminal transactivation domain of p53 (residues 37–57; p53N) and, by using NMR spectroscopy, characterize two mechanisms by which the RPA/p53 interaction can be modulated. RPA70N forms an oligonucleotide/oligosaccharide-binding fold, similar to that previously observed for the ssDNA-binding domains of RPA. In contrast, the N-terminal p53 transactivation domain is largely disordered in solution, but residues 37–57 fold into two amphipathic helices, H1 and H2, upon binding with RPA70N. The H2 helix of p53 structurally mimics the binding of ssDNA to the oligonucleotide/oligosaccharide-binding fold. NMR experiments confirmed that both ssDNA and an acidic peptide mimicking a phosphorylated form of RPA32N can independently compete the acidic p53N out of the binding site. Taken together, our data suggest a mechanism for DNA damage signaling that can explain a threshold response to DNA damage.

Bibliography

Bochkareva, E., Kaustov, L., Ayed, A., Yi, G.-S., Lu, Y., Pineda-Lucena, A., Liao, J. C. C., Okorokov, A. L., Milner, J., Arrowsmith, C. H., & Bochkarev, A. (2005). Single-stranded DNA mimicry in the p53 transactivation domain interaction with replication protein A. Proceedings of the National Academy of Sciences, 102(43), 15412â15417.

Authors 11

Elena Bochkareva (first)
Lilia Kaustov (additional)
Ayeda Ayed (additional)
Gwan-Su Yi (additional)
Ying Lu (additional)
Antonio Pineda-Lucena (additional)
Jack C. C. Liao (additional)
Andrei L. Okorokov (additional)
Jo Milner (additional)
Cheryl H. Arrowsmith (additional)
Alexey Bochkarev (additional)

References 49 Referenced 245

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Dates

Type	When
Created	19 years, 10 months ago (Oct. 17, 2005, 8:34 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 2:05 p.m.)
Indexed	4 weeks, 1 day ago (July 30, 2025, 10:09 a.m.)
Issued	19 years, 10 months ago (Oct. 17, 2005)
Published	19 years, 10 months ago (Oct. 17, 2005)
Published Online	19 years, 10 months ago (Oct. 17, 2005)
Published Print	19 years, 10 months ago (Oct. 25, 2005)

Funders 0

None

BibTeX

@article{Bochkareva_2005, title={Single-stranded DNA mimicry in the p53 transactivation domain interaction with replication protein A}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0504614102}, DOI={10.1073/pnas.0504614102}, number={43}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Bochkareva, Elena and Kaustov, Lilia and Ayed, Ayeda and Yi, Gwan-Su and Lu, Ying and Pineda-Lucena, Antonio and Liao, Jack C. C. and Okorokov, Andrei L. and Milner, Jo and Arrowsmith, Cheryl H. and Bochkarev, Alexey}, year={2005}, month=oct, pages={15412–15417} }

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