title: The Identification of a Novel Mutant Allele of topoisomerase II in Caenorhabditis elegans Reveals a Unique Role in Chromosome Segregation During Spermatogenesis.
abstract: Topoisomerase II alleviates DNA entanglements that are generated during mitotic DNA replication, transcription, and sister chromatid separation. In contrast to mitosis, meiosis has two rounds of chromosome segregation following one round of DNA replication. In meiosis II, sister chromatids segregate from each other, similar to mitosis. Meiosis I, on the other hand, segregates homologs, which requires pairing, synapsis, and recombination. The exact role that topoisomerase II plays during meiosis is unknown. In a screen reexamining Caenorhabditis elegans legacy mutants isolated 30 years ago, we identified a novel allele of the gene encoding topoisomerase II, top-2(it7). In this study, we demonstrate that top-2(it7) males produce dead embryos, even when fertilizing wild-type oocytes. Characterization of early embryonic events indicates that fertilization is successful and sperm components are transmitted to the embryo. However, sperm chromatin is not detected in these fertilized embryos. Examination of top-2(it7) spermatogenic germ lines reveals that the sperm DNA fails to segregate properly during anaphase I of meiosis, resulting in anucleate sperm. top-2(it7) chromosome-segregation defects observed during anaphase I are not due to residual entanglements incurred during meiotic DNA replication and are not dependent on SPO-11-induced double-strand DNA breaks. Finally, we show that TOP-2 associates with chromosomes in meiotic prophase and that chromosome association is disrupted in the germ lines of top-2(it7) mutants.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 jaramillolamban@mail.nih.gov.
authors.forename: Aimee
authors.initials: A
authors.lastname: Jaramillo-Lambert
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Fabritius
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Hansen
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Harold E
authors.initials: HE
authors.lastname: Smith
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Andy
authors.initials: A
authors.lastname: Golden
mesh_terms: D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D020090:Chromosome Segregation; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008297:Male; D008540:Meiosis; D009154:Mutation; D013091:Spermatogenesis
chemical_list: D029742:Caenorhabditis elegans Proteins; D004250:DNA Topoisomerases, Type II
keywords: Caenorhabditis elegans; meiosis; spermatogenesis; top-2; topoisomerase II