The FK506 binding protein Fpr3 counteracts protein phosphatase 1 to maintain meiotic recombination checkpoint activity.
The meiotic recombination checkpoint delays gamete precursors in G2 until DNA breaks created during recombination are repaired and chromosome structure has been restored. Here, we show that the FK506 binding protein Fpr3 prevents premature adaptation to damage and thus serves to maintain recombination checkpoint activity. Impaired checkpoint function is observed both in cells lacking FPR3 and in cells treated with rapamycin, a small molecule inhibitor that binds to the proline isomerase (PPIase) domain of Fpr3. FPR3 functions in the checkpoint through controlling protein phosphatase 1 (PP1). Fpr3 interacts with PP1 through its PPIase domain, regulates PP1 localization, and counteracts the activity of PP1 in vivo. Our findings define a branch of the recombination checkpoint involved in the adaptation to persistent chromosomal damage and a critical function for FK506 binding proteins during meiosis.
Hochwagen
Andreas
A
Center for Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, E17-233, 40 Ames Street, Cambridge, Massachusetts 02139, USA.
Tham
Wai-Hong
WH
Brar
Gloria A
GA
Amon
Angelika
A
D004249:DNA Damage; D005786:Gene Expression Regulation; D020104:Immunophilins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008540:Meiosis; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D017354:Point Mutation; D054645:Protein Phosphatase 1; D011995:Recombination, Genetic / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D013997:Time Factors
D029701:Saccharomyces cerevisiae Proteins; C092048:GLC7 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C403327:FPR3 protein, S cerevisiae; D020104:Immunophilins; D019696:Peptidylprolyl Isomerase; D020123:Sirolimus