HETEROCHROMATIN PROTEIN-1 IS REQUIRED FOR CORRECT CHROMOSOME SEGREGATION IN DROSOPHILA EMBRYOS

Heterochromatin protein 1 is associated with centromeric heterochromat in in Drosophila, mice, and humans, Loss of function mutations in the gene encoding heterochromatin protein 1 in Drosophila, Suppressor of v ariegation2-5, 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-e ffect variegation, but also cause recessive embryonic lethality, In th is study, we analyze the latter phenotype in the hope of gaining insig ht into heterochromatin function. In our analyses of four alleles of S uppressor of variegation2-5, the lethality was found to be associated with defects in chromosome morphology and segregation. While some of t hese defects are seen throughout embryonic development, both the frequ ency and severity of the defects are greatest between cycles 10 and 14 when zygotic transcription of the Suppressor of variegation2-5 gene a pparently begins, By this time in development, heterochromatin protein 1 levels are diminished by four-fold in a quarter of the embryos prod uced by parents that are both heterozygous for a null allele (Suppress or of variegation2-5(05)). In a live analysis of the phenotype, we fin d prophase to be lengthened by more than two-fold in Suppressor of var iegation2-5(05) mutant embryos with subsequent defects in chromosome s egregation, The elongated prophase suggests that the segregation pheno type 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 centromorespecific antigen indicates that the kinetochores of most chromosomes are functional, T he immunostaining results are more consistent with defects in chromoso me condensation being responsible for the segregation phenotype.