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Transcription coactivator p300 binds PCNA and may have a role in DNA repair synthesis

Nature volume 410, pages 387–391 (2001)Cite this article

Abstract

The transcriptional coactivator p300 interacts with many transcription factors that participate in a broad spectrum of biological activities, such as cellular differentiation, homeostasis and growth control1,2. Mouse embryos lacking both p300 alleles die around mid-gestation, with pleiotropic defects in morphogenesis, in cell differentiation and, unexpectedly, in cell proliferation because of reduced DNA synthesis3. Here we show that p300 may have a role in DNA repair synthesis through its interaction with proliferating cell nuclear antigen (PCNA). We show that in vitro and in vivo p300 forms a complex with PCNA that does not depend on the S phase of cell cycle. A large fraction of both p300 and PCNA colocalize to speckled structures in the nucleus. Furthermore, the endogenous p300–PCNA complex stimulates DNA synthesis in vitro. Chromatin immunoprecipitation experiments indicate that p300 is associated with freshly synthesized DNA after ultraviolet irradiation. Our results suggest that p300 may participate in chromatin remodelling at DNA lesion sites to facilitate PCNA function in DNA repair synthesis.

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Figure 1: PCNA form a complex.
Figure 2: Colocalization of p300 and PCNA in HeLa cells in vivo.
Figure 3: Mapping of the PCNA interaction domain in p300.
Figure 4: p300 is associated with freshly repaired DNA.

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Acknowledgements

We thank M. Stucki and Z. Jonsson for pol δ, and wild-type and mutant PCNA; U. Hübscher for critically reading the manuscript; other members of the Institute of Veterinary Biochemistry for helpful advice; and U. Ziegler, S. Koundrioukoff and M.Y. Nakano for technical help. This work was supported in part by the Swiss National Science Foundation (S.H. and P.O.H.), the UBS AG “im Auftrag eines Kunden” (R.I.) and the Olga Mayenfisch Stiftung. M.O.H. is supported by the Kanton of Zürich.

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  1. Institute of Veterinary Biochemistry, University of Zürich, Winterthurerstrasse 190, Zürich, 8057, Switzerland

    Sameez Hasan, Paul O. Hassa, Ralph Imhof & Michael O. Hottiger

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  1. Sameez Hasan
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  2. Paul O. Hassa
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Correspondence to Michael O. Hottiger.

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Hasan, S., Hassa, P., Imhof, R. et al. Transcription coactivator p300 binds PCNA and may have a role in DNA repair synthesis. Nature 410, 387–391 (2001). https://doi.org/10.1038/35066610

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