PgmNr W445: top-2 is required for proper chromosome segregation during male meiosis in C. elegans.

Authors:
A. N. Jaramillo-Lambert; H. Smith; A. Golden


Institutes
NIDDK/NIH, Bethesda, MD.


Keyword: Dosage compensation, cells, Meiosis Recombination

Abstract:

Type II DNA topoisomerases play a critical role in chromosome fidelity by alleviating topological stresses that arise within chromosomes. Topo II is a large ATP-dependent homodimeric enzyme. Each subunit breaks one DNA strand, passes a second unbroken strand through the break, and then reseals the break. Thus, during mitotic divisions, Topo II enzymes solve topological problems that arise during replication, transcription, sister chromatid segregation, and recombination. In contrast to the single round of DNA replication followed by a single nuclear division during mitosis, meiosis has one round of DNA replication followed by two nuclear divisions. 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. Studies in mammals, yeast, and Drosophila have demonstrated that Topo II plays a role in homologous chromosome segregation at meiosis I. However, the exact role Topo II plays during meiosis is unknown. In a screen re-examining temperature sensitive legacy mutants identified thirty years ago, we identified a C. elegans allele of Topo II, top-2(it7ts). Initial analysis found that top-2(it7ts) mutant males produce dead embryos, even when fertilizing wild-type oocytes. Characterization of early embryonic events indicates fertilization is successful and that sperm components (e.g. centrosomes) are transmitted to the embryo. However, sperm chromatin is not detected in these fertilized embryos. Examination of top-2(it7ts) male germ lines revealed that the sperm DNA fails to properly segregate during the meiotic divisions. Chromatin bridges form during anaphase I and the chromatin becomes trapped in the residual body. Failure to segregate DNA into the spermatids results in anucleate sperm that are capable of fertilization; early embryonic events appear normal but embryos arrest around the 200-cell stage. top-2 (it7ts) chromosome segregation defects observed during anaphase I are not due to residual entanglements incurred during meiotic DNA replication and are not a consequence of recombination defects. We are currently evaluating the role of top-2 in chromosome structure.



Wormbase Genetic Index
1. top-2