Hbo1 links p53-dependent stress signaling to DNA replication licensing

Masayoshi Iizuka, Olga F. Sarmento, Takao Sekiya, Heidi Scrable, C. David Allis, M. Mitchell Smith

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Hbo1 is a histone acetyltransferase (HAT) that is required for global histone H4 acetylation, steroid-dependent transcription, and chromatin loading of MCM2-7 during DNA replication licensing. It is the catalytic subunit of protein complexes that include ING and JADE proteins, growth regulatory factors and candidate tumor suppressors. These complexes are thought to act via tumor suppressor p53, but the molecular mechanisms and links between stress signaling and chromatin, are currently unknown. Here, we show that p53 physically interacts with Hbo1 and negatively regulates its HAT activity in vitro and in cells. Two physiological stresses that stabilize p53, hyperosmotic shock and DNA replication fork arrest, also inhibit Hbo1 HAT activity in a p53-dependent manner. Hyperosmotic stress during G1 phase specifically inhibits the loading of the MCM2-7 complex, providing an example of the chromatin output of this pathway. These results reveal a direct regulatory connection between p53-responsive stress signaling and Hbo1-dependent chromatin pathways.

Original languageEnglish (US)
Pages (from-to)140-153
Number of pages14
JournalMolecular and cellular biology
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Iizuka, M., Sarmento, O. F., Sekiya, T., Scrable, H., Allis, C. D., & Smith, M. M. (2008). Hbo1 links p53-dependent stress signaling to DNA replication licensing. Molecular and cellular biology, 28(1), 140-153. https://doi.org/10.1128/MCB.00662-07