The Drosophila Su(var)2-10 locus regulates chromosome structure and function and encodes a member of the PIAS protein family

The conserved heterochromatic location of centromeres in higher eukaryotes suggests that intrinsic properties of heterochromatin are important for chr omosome inheritance. Based on this hypothesis, mutations in Drosophila mela nogaster that alter heterochromatin-induced gene silencing were tested for effects on chromosome inheritance. Here we describe the characterization of the Su(var)2-10 locus, initially identified as a Suppressor of Position-Ef fect Variegation. Su(var)2-10 is required for viability, and mutations caus e both minichromosome and endogenous chromosome inheritance defects. Mitoti c chromosomes are improperly condensed in mutants, and polytene chromosomes are structurally abnormal and disorganized in the nucleus. Su(var)2-10 enc odes a member of the PIAS protein family, a group of highly conserved prote ins that control diverse functions. SU(VAR)2-10 proteins colocalize with nu clear lamin in interphase, and little to no SU(VAR)2-10 is found on condens ed mitotic chromosomes. SU(VAR)2-10 is present at some polytene chromosome telomeres, and FISH analyses in mutant polytene nuclei revealed defects in telomere clustering and telomere-nuclear-lamina associations. We propose th at Su(var2-10 controls multiple aspects of chromosome structure and functio n by establishing/maintaining chromosome organization in interphase nuclei.