title: The fidelity of synaptonemal complex assembly is regulated by a signaling mechanism that controls early meiotic progression.
abstract: Proper chromosome segregation during meiosis requires the assembly of the synaptonemal complex (SC) between homologous chromosomes. However, the SC structure itself is indifferent to homology, and poorly understood mechanisms that depend on conserved HORMA-domain proteins prevent ectopic SC assembly. Although HORMA-domain proteins are thought to regulate SC assembly as intrinsic components of meiotic chromosomes, here we uncover a key role for nuclear soluble HORMA-domain protein HTP-1 in the quality control of SC assembly. We show that a mutant form of HTP-1 impaired in chromosome loading provides functionality of an HTP-1-dependent checkpoint that delays exit from homology search-competent stages until all homolog pairs are linked by the SC. Bypassing of this regulatory mechanism results in premature meiotic progression and licensing of homology-independent SC assembly. These findings identify nuclear soluble HTP-1 as a regulator of early meiotic progression, suggesting parallels with the mode of action of Mad2 in the spindle assembly checkpoint.
authors.affiliation: Meiosis Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Silva
authors.affiliation: Meiosis Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Nuria
authors.initials: N
authors.lastname: Ferrandiz
authors.affiliation: Meiosis Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Barroso
authors.affiliation: DNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Silvia
authors.initials: S
authors.lastname: Tognetti
authors.affiliation: Meiosis Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: James
authors.initials: J
authors.lastname: Lightfoot
authors.affiliation: Meiosis Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Oana
authors.initials: O
authors.lastname: Telecan
authors.affiliation: Proteomics Facility, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Vesela
authors.initials: V
authors.lastname: Encheva
authors.affiliation: Proteomics Facility, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Faull
authors.affiliation: Department of Biochemistry, Oxford University, Oxford OX1 3QU, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Hanni
authors.affiliation: Department of Biochemistry, Oxford University, Oxford OX1 3QU, UK.
authors.forename: Andre
authors.initials: A
authors.lastname: Furger
authors.affiliation: Proteomics Facility, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Ambrosius P
authors.initials: AP
authors.lastname: Snijders
authors.affiliation: DNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Speck
authors.affiliation: Meiosis Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK. Electronic address: enrique.martinez-perez@imperial.ac.uk.
authors.forename: Enrique
authors.initials: E
authors.lastname: Martinez-Perez
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D023902:Chromosome Pairing / Q000235:genetics*; D020090:Chromosome Segregation / Q000502:physiology; D008540:Meiosis / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013573:Synaptonemal Complex / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins