Involvement of human MOF in ATM function

Arun Gupta, Girdhar G. Sharma, Charles S H Young, Manjula Agarwal, Edwin R. Smith, Tanya T. Paull, John C. Lucchesi, Kum Kum Khanna, Thomas Ludwig, Tej K. Pandita

Research output: Contribution to journalArticlepeer-review

172 Scopus citations

Abstract

We have determined that hMOF, the human ortholog of the Drosophila MOF gene (males absent on the first), encoding a protein with histone acetyltransferase activity, interacts with the ATM (ataxia-telangiectasia-mutated) protein. Cellular exposure to ionizing radiation (IR) enhances hMOF-dependent acetylation of its target substrate, lysine 16 (K16) of histone H4 independently of ATM function. Blocking the IR-induced increase in acetylation of histone H4 at K16, either by the expression of a dominant negative mutant ΔhMOF or by RNA interference-mediated hMOF knockdown, resulted in decreased ATM autophosphorylation, ATM kinase activity, and the phosphorylation of downstream effectors of ATM and DNA repair while increasing cell killing. In addition, decreased hMOF activity was associated with loss of the cell cycle checkpoint response to DNA double-strand breaks. The overexpression of wild-type hMOF yielded the opposite results, i.e., a modest increase in cell survival and enhanced DNA repair after IR exposure. These results suggest that hMOF influences the function of ATM.

Original languageEnglish (US)
Pages (from-to)5292-5305
Number of pages14
JournalMolecular and cellular biology
Volume25
Issue number12
DOIs
StatePublished - Jun 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Involvement of human MOF in ATM function'. Together they form a unique fingerprint.

Cite this