Progression of meiotic DNA replication is modulated by interchromosomal interaction proteins, negatively by Spo11p and positively by Rec8p

  1. Rita S. Cha1,
  2. Beth M. Weiner1,
  3. Scott Keeney2,
  4. Job Dekker1, and
  5. N. Kleckner1,3
  1. 1Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138 USA; 2Program in Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, New York USA 10021

Abstract

Spo11p is a key mediator of interhomolog interactions during meiosis. Deletion of the SPO11 gene decreases the length of S phase by ∼25%. Rec8p is a key coordinator of meiotic interhomolog and intersister interactions. Deletion of the REC8 gene increases S-phase length, by ∼10% in wild-type and ∼30% in aspo11Δ background. Thus, the progression of DNA replication is modulated by interchromosomal interaction proteins. Thespo11–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.

Keywords

Footnotes

  • 3 Corresponding author.

  • E-MAIL kleckner{at}fas.harvard.edu; FAX (617) 495-0758.

    • Received October 14, 1999.
    • Accepted January 4, 2000.
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