From fertilization to cancer: the role of centrosomes in the union and separation of genomic material.
Centrosomes play crucial roles in the union of sperm and egg nuclei during fertilization and in the equal separation of genomic material during cell division. While many studies in recent years have focused on the molecular composition of centrosomes, this article focuses on the structural behavior of centrosomes and on factors that play a role in centrosome functions under normal, artificially altered, and abnormal conditions. We review here how studies in the classic sea urchin egg model have contributed to our knowledge on the centrosome cycle within the cell cycle, on compaction and decompaction of centrosomal material, and on the contributions of maternal and paternal centrosomes during fertilization. Centrosome material is activated in unfertilized eggs by increasing pH with ammonium and by increasing calcium with the ionophore A23187, which are conditions that are normally induced by sperm. D(2)O and taxol also induce centrosome aggregation in the unfertilized egg. Maternal and paternal centrosome material both contribute to the formation of a functional centrosome but the formation of a bipolar centrosome requires material from the paternal centrosome. Fertilization of taxol-treated eggs reveals that the male centrosome possesses the capability to attract maternal centrosome material. When pronuclear fusion of the male and female pronuclei is inhibited with agents such as the disulfide reducing agent dithiothreitol (DTT) a bipolar mitotic apparatus is formed from the paternal centrosome. Furthermore, one centrosome of the bipolar mitotic apparatus is capable of organizing an additional half spindle that attaches to the female pronucleus indicating a functional and perhaps structural connection between centrosomes and chromatin. Sea urchin eggs are also useful to study centrosome abnormalities and consequences for the cell cycle. While classic studies by Theodor Boveri have shown that dispermic fertilization will result in abnormal cell division because of multiple centrosomes contributed by sperm, abnormal cell division can also be induced by chemical alterations of centrosomes. Compaction and decompaction of centrosome structure is studied using chloral hydrate or the chaotropic agent formamide, which reveals that centrosomes can be chemically altered to produce mono- or multipolar abnormal mitosis and unequal distribution of genomic material upon release from formamide. The patterns of abnormal centrosome reformations after recovery from formamide treatment resemble those seen in cancer cells which argues that structural defects of centrosomes can account for the formation of abnormal mitosis and multipolar cells frequently observed in cancer. In summary, the sea urchin model has been most useful to gain information on the role of centrosomes during fertilization and cell division as well as on adverse conditions that play a role in centrosome dysfunctions and in disease.
Schatten
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Department of Veterinary Pathobiology, University of Missouri-Columbia, 65211, USA. SchattenH@missouri.edu
Hueser
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Chakrabarti
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D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D018385:Centrosome / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D002869:Chromosome Aberrations; D004247:DNA / Q000032:analysis; D004229:Dithiothreitol / Q000494:pharmacology; D005306:Fertilization / Q000187:drug effects / Q000502:physiology*; D005559:Formamides; D006863:Hydrogen-Ion Concentration; D008297:Male; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D010063:Ovum / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds; D012617:Sea Urchins; D013094:Spermatozoa / Q000187:drug effects / Q000648:ultrastructure
D005559:Formamides; D000644:Quaternary Ammonium Compounds; D000001:Calcimycin; C031066:formamide; D004247:DNA; D017239:Paclitaxel; D004229:Dithiothreitol