Nucleic Acids Research Advance Access published online on March 29, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn037
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Molecular Biology |
Distinct regions of ATF/CREB proteins Atf1 and Pcr1 control recombination hotspot ade6–M26 and the osmotic stress response
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 West Markham Street (slot 516) Little Rock, AR 72205-7199, USA
*To whom correspondence should be addressed. Tel: +(501) 686 5787; Fax: +(501) 526 7008; Email: wahlswaynep{at}uams.edu
Received December 19, 2007. Revised January 17, 2008. Accepted January 21, 2008.
The Atf1 protein of Schizosaccharomyces pombe contains a bZIP (DNA-binding/protein dimerization) domain characteristic of ATF/CREB proteins, but no other functional domains or clear homologs have been reported. Atf1-containing, bZIP protein dimers bind to CRE-like DNA sites, regulate numerous stress responses, and activate meiotic recombination at hotspots like ade6–M26. We defined systematically the organization of Atf1 and its heterodimer partner Pcr1, which is required for a subset of Atf1-dependent functions. Surprisingly, only the bZIP domain of Pcr1 is required for hotspot activity and tethering of Atf1 to ade6 promotes recombination in the absence of its bZIP domain and the Pcr1 protein. Therefore the recombination–activation domain of Atf1-Pcr1 heterodimer resides exclusively in Atf1, and Pcr1 confers DNA-binding site specificity in vivo. Atf1 has a modular organization in which distinct regions affect differentially the osmotic stress response (OSA) and meiotic recombination (HRA, HRR). The HRA and HRR regions are necessary and sufficient to activate and repress recombination, respectively. Moreover, Atf1 defines a family of conserved proteins with discrete sequence motifs in the functional domains (OSA, HRA, HRR, bZIP). These findings reveal the functional organization of Atf1 and Pcr1, and illustrate several mechanisms by which bZIP proteins can regulate multiple, seemingly disparate activities.