title: Progression of meiotic DNA replication is modulated by interchromosomal interaction proteins, negatively by Spo11p and positively by Rec8p.
abstract: Spo11p is a key mediator of interhomolog interactions during meiosis. Deletion of the SPO11 gene decreases the length of S phase by approximately 25%. Rec8p is a key coordinator of meiotic interhomolog and intersister interactions. Deletion of the REC8 gene increases S-phase length, by approximately 10% in wild-type and approximately 30% in a spo11Delta background. Thus, the progression of DNA replication is modulated by interchromosomal interaction proteins. The spo11-Y135F DSB (double strand break) catalysis-defective mutant is normal for S-phase modulation and DSB-independent homolog pairing but is defective for later events, formation of DSBs, and synaptonemal complexes. Thus, earlier and later functions of Spo11 are defined. We propose that meiotic S-phase progression is linked directly to development of specific chromosomal features required for meiotic interhomolog interactions and that this feedback process is built upon a more fundamental mechanism, common to all cell types, by which S-phase progression is coupled to development of nascent intersister connections and/or related aspects of chromosome morphogenesis. Roles for Rec8 and/or Spo11 in progression through other stages of meiosis are also revealed.
authors.affiliation: Department of Molecular Biology, Harvard University, Cambridge, Massachusetts 02138 USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Cha
authors.forename: B M
authors.initials: BM
authors.lastname: Weiner
authors.forename: S
authors.initials: S
authors.lastname: Keeney
authors.forename: J
authors.initials: J
authors.lastname: Dekker
authors.forename: N
authors.initials: N
authors.lastname: Kleckner
mesh_terms: D015825:Chromosomes, Fungal / Q000502:physiology* / Q000648:ultrastructure; D004261:DNA Replication / Q000502:physiology*; D004706:Endodeoxyribonucleases; D004950:Esterases / Q000235:genetics / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D008540:Meiosis / Q000502:physiology*; D010750:Phosphoproteins; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins; D000099257:Meiotic Recombination Protein SPO11; D000097722:Cohesins
chemical_list: D004706:Endodeoxyribonucleases; D004950:Esterases; D005656:Fungal Proteins; D010750:Phosphoproteins; D029702:Schizosaccharomyces pombe Proteins; D000099257:Meiotic Recombination Protein SPO11; C077081:REC8 protein, S pombe; D000097722:Cohesins