Phosphorylation-independent regulation of Atf1-promoted meiotic recombination by stress-activated, p38 kinase Spc1 of fission yeast.
BACKGROUND
Stress-activated protein kinases regulate multiple cellular responses to a wide variety of intracellular and extracellular conditions. The conserved, multifunctional, ATF/CREB protein Atf1 (Mts1, Gad7) of fission yeast binds to CRE-like (M26) DNA sites. Atf1 is phosphorylated by the conserved, p38-family kinase Spc1 (Sty1, Phh1) and is required for many Spc1-dependent stress responses, efficient sexual differentiation, and activation of Rec12 (Spo11)-dependent meiotic recombination hotspots like ade6-M26.


RESULTS
We sought to define mechanisms by which Spc1 regulates Atf1 function at the ade6-M26 hotspot. The Spc1 kinase was essential for hotspot activity, but dispensable for basal recombination. Unexpectedly, a protein lacking all eleven MAPK phospho-acceptor sites and detectable phosphorylation (Atf1-11M) was fully proficient for hotspot recombination. Furthermore, tethering of Atf1 to ade6 in the chromosome by a heterologous DNA binding domain bypassed the requirement for Spc1 in promoting recombination.


CONCLUSIONS
The Spc1 protein kinase regulates the pathway of Atf1-promoted recombination at or before the point where Atf1 binds to chromosomes, and this pathway regulation is independent of the phosphorylation status of Atf1. Since basal recombination is Spc1-independent, the principal function of the Spc1 kinase in meiotic recombination is to correctly position Atf1-promoted recombination at hotspots along chromosomes. We also propose new hypotheses on regulatory mechanisms for shared (e.g., DNA binding) and distinct (e.g., osmoregulatory vs. recombinogenic) activities of multifunctional, stress-activated protein Atf1.
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Jun
J
Gao
Mari K
MK
Davidson
Wayne P
WP
Wahls
D051697:Activating Transcription Factor 1 / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D004271:DNA, Fungal / Q000737:chemistry / Q000378:metabolism; D008540:Meiosis / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011995:Recombination, Genetic; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D051697:Activating Transcription Factor 1; D004271:DNA, Fungal; D010750:Phosphoproteins; D029702:Schizosaccharomyces pombe Proteins; C106740:atf1 protein, S pombe; D020928:Mitogen-Activated Protein Kinases; C524689:Spc1 protein, S pombe; D048051:p38 Mitogen-Activated Protein Kinases