Reference - PMID:19436749 - Phosphorylation-independent regulation of Atf1-promoted meiotic recombination by stress-activated, p38 kinase Spc1 of fission yeast.
Reference summary
- PubMed ID
- PMID:19436749
- Title
- Phosphorylation-independent regulation of Atf1-promoted meiotic recombination by stress-activated, p38 kinase Spc1 of fission yeast.
- Authors
- Gao J, Davidson MK, Wahls WP
- Citation
- PLoS One 2009;4(5):e5533
- Publication year
- 2009
- Abstract
- 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.
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.
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.
Annotation
Single locus phenotype
Genes:
Genotypes:
- atf1-11M-T77A(S2A,S4A,T77A,S140A,S152A,S172A,T204I,T216I,S226A,T249I,S438A aa)