The FK506 binding protein Fpr3 counteracts protein phosphatase 1 to maintain meiotic recombination checkpoint activity

Andreas Hochwagen, Wai Hong Tham, Gloria A. Brar, Angelika Amon

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)861-873
Number of pages13
JournalCell
Volume122
Issue number6
DOIs
StatePublished - Sep 23 2005

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Tacrolimus Binding Proteins
Protein Phosphatase 1
Peptidylprolyl Isomerase
Genetic Recombination
Chromosome Structures
DNA Breaks
Meiosis
Sirolimus
Chromosomes
Germ Cells
Molecules
DNA

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

The FK506 binding protein Fpr3 counteracts protein phosphatase 1 to maintain meiotic recombination checkpoint activity. / Hochwagen, Andreas; Tham, Wai Hong; Brar, Gloria A.; Amon, Angelika.

In: Cell, Vol. 122, No. 6, 23.09.2005, p. 861-873.

Research output: Contribution to journalArticle

Hochwagen, Andreas ; Tham, Wai Hong ; Brar, Gloria A. ; Amon, Angelika. / The FK506 binding protein Fpr3 counteracts protein phosphatase 1 to maintain meiotic recombination checkpoint activity. In: Cell. 2005 ; Vol. 122, No. 6. pp. 861-873.
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