title: Heterochromatin protein 1 is required for correct chromosome segregation in Drosophila embryos.
abstract: Heterochromatin protein 1 is associated with centromeric heterochromatin in Drosophila, mice, and humans. Loss of function mutations in the gene encoding heterochromatin protein 1 in Drosophila, Suppressor of variegation2-5, decrease the mosaic repression observed for euchromatic genes that have been juxtaposed to centromeric heterochromatin. These heterochromatin protein 1 mutations not only suppress this position-effect variegation, but also cause recessive embryonic lethality. In this study, we analyze the latter phenotype in the hope of gaining insight into heterochromatin function. In our analyses of four alleles of Suppressor of variegation2-5, the lethality was found to be associated with defects in chromosome morphology and segregation. While some of these defects are seen throughout embryonic development, both the frequency and severity of the defects are greatest between cycles 10 and 14 when zygotic transcription of the Suppressor of variegation2-5 gene apparently begins. By this time in development, heterochromatin protein 1 levels are diminished by four-fold in a quarter of the embryos produced by parents that are both heterozygous for a null allele (Suppressor of variegation2-5(05)). In a live analysis of the phenotype, we find prophase to be lengthened by more than two-fold in Suppressor of variegation2-5(05) mutant embryos with subsequent defects in chromosome segregation. The elongated prophase suggests that the segregation phenotype is a consequence of defects in events that occur during prophase, either in chromosome condensation or kinetochore assembly or function. Immunostaining with an antibody against a centromerespecific antigen indicates that the kinetochores of most chromosomes are functional. The immunostaining results are more consistent with defects in chromosome condensation being responsible for the segregation phenotype.
authors.affiliation: Department of Biochemistry and Biophysics, University of California at San Francisco 94143-0448, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kellum
authors.forename: B M
authors.initials: BM
authors.lastname: Alberts
mesh_terms: D000483:Alleles; D000818:Animals; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D003433:Crosses, Genetic; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D017344:Genes, Insect; D005804:Genes, Lethal; D016153:Genes, Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D010641:Phenotype; D011418:Prophase
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D000090266:Chromobox Protein Homolog 5