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Eukaryotic Cell, April 2003, p. 306-317, Vol. 2, No. 2
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.2.306-317.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Saccharomyces cerevisiae Dap1p, a Novel DNA Damage Response Protein Related to the Mammalian Membrane-Associated Progesterone Receptor

Randal A. Hand,1 Nan Jia,2 Martin Bard,2 and Rolf J. Craven1*

Department of Surgery, Division of Surgical Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599,1 Department of Biology, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana 462022

Received 3 September 2002/ Accepted 23 December 2002

The response to damage is crucial for cellular survival, and eukaryotic cells require a broad array of proteins for an intact damage response. We have found that the YPL170W (DAP1 [for damage response protein related to membrane-associated progesterone receptors]) gene is required for growth in the presence of the methylating agent methyl methanesulfonate (MMS). The DAP1 open reading frame shares homology with a broadly conserved family of membrane-associated progesterone receptors (MAPRs). Deletion of DAP1 leads to sensitivity to MMS, elongated telomeres, loss of mitochondrial function, and partial arrest in sterol synthesis. Sensitivity of dap1 strains to MMS is not due to loss of damage checkpoints. Instead, dap1 cells are arrested as unbudded cells after MMS treatment, suggesting that Dap1p is required for cell cycle progression following damage. Dap1p also directs resistance to itraconazole and fluconazole, inhibitors of sterol synthesis. We have found that dap1 cells have slightly decreased levels of ergosterol but increased levels of the ergosterol intermediates squalene and lanosterol, indicating that dap1 cells have a partial defect in sterol synthesis. This is the first evidence linking a MAPR family member to sterol regulation or the response to damage, and these functions are probably conserved in a variety of eukaryotes.

* Corresponding author. Mailing address: 21-237 Lineberger Comprehensive Cancer Center, Campus Box 7295, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295. Phone: (919) 966-7834. Fax: (919) 966-8212. E-mail: rolf{at}email.unc.edu.

Eukaryotic Cell, April 2003, p. 306-317, Vol. 2, No. 2
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.2.306-317.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Craven, R. J., Mallory, J. C., Hand, R. A. (2007). Regulation of Iron Homeostasis Mediated by the Heme-binding Protein Dap1 (Damage Resistance Protein 1) via the P450 Protein Erg11/Cyp51. J. Biol. Chem. 282: 36543-36551 [Abstract] [Full Text]  
  • Crudden, G., Chitti, R. E., Craven, R. J. (2006). Hpr6 (Heme-1 Domain Protein) Regulates the Susceptibility of Cancer Cells to Chemotherapeutic Drugs. J. Pharmacol. Exp. Ther. 316: 448-455 [Abstract] [Full Text]  
  • Mallory, J. C., Crudden, G., Johnson, B. L., Mo, C., Pierson, C. A., Bard, M., Craven, R. J. (2005). Dap1p, a Heme-Binding Protein That Regulates the Cytochrome P450 Protein Erg11p/Cyp51p in Saccharomyces cerevisiae. Mol. Cell. Biol. 25: 1669-1679 [Abstract] [Full Text]  


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