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

Sameez Hasan, Paul O. Hassa, Ralph Imhof and Michael O. Hottiger ()
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Sameez Hasan: Institute of Veterinary Biochemistry, University of Zürich
Paul O. Hassa: Institute of Veterinary Biochemistry, University of Zürich
Ralph Imhof: Institute of Veterinary Biochemistry, University of Zürich
Michael O. Hottiger: Institute of Veterinary Biochemistry, University of Zürich

Nature, 2001, vol. 410, issue 6826, 387-391

Abstract: 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.

Date: 2001
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DOI: 10.1038/35066610

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