Nuclear reorganization and homologous chromosome pairing during meiotic prophase require C. elegans chk-2.
Analysis of mutants defective in meiotic chromosome pairing has uncovered a role for Caenorhabditis elegans chk-2 in initial establishment of pairing between homologous chromosomes during early meiotic prophase. chk-2 is also required for the major spatial reorganization of nuclei that normally accompanies the onset of pairing, suggesting a mechanistic coupling of these two events. Despite failures in pairing, nuclear reorganization, and crossover recombination, chk-2 mutants undergo many other aspects of meiotic chromosome morphogenesis and complete gametogenesis. Although chk-2 encodes a C. elegans ortholog of the Cds1/Chk2 checkpoint protein kinases, germ-line nuclei in chk-2 mutants are competent to arrest proliferation in response to replication inhibition and to trigger DNA damage checkpoint responses to ionizing radiation. However, chk-2 mutants are defective in triggering the pachytene DNA damage checkpoint in response to an intermediate block in the meiotic recombination pathway, suggesting that chk-2 is required either for initiation of meiotic recombination or for monitoring a specific subset of DNA damage lesions. We propose that chk-2 functions during premeiotic S phase to enable chromosomes to become competent for subsequent meiotic prophase events and/or to coordinate replication with entry into prophase.
MacQueen
A J
AJ
Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305-5329, USA.
Villeneuve
A M
AM
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D002467:Cell Nucleus / Q000502:physiology; D064447:Checkpoint Kinase 2; D002875:Chromosomes / Q000502:physiology; D004249:DNA Damage; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D005854:Germ Cells / Q000502:physiology; D008540:Meiosis / Q000502:physiology*; D011418:Prophase / Q000502:physiology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D051135:Rad51 Recombinase; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; D051135:Rad51 Recombinase; C495148:rad-51 protein, C elegans