Mutations in the Insulator Protein Suppressor of Hairy Wing Induce Genome Instability

Abstract

Chromatin insulator proteins mediate the formation of contacts between distant insulator sites along chromatin fibers. Long-range contacts facilitate communication between regulatory sequences and gene promoters throughout the genome, allowing accurate gene transcription regulation during embryo development and cell differentiation. Lack of insulator function has detrimental effects often resulting in lethality. The Drosophila insulator protein Suppressor of Hairy wing [Su(Hw)] is not essential for viability, but plays a crucial role in female oogenesis. The mechanism(s) by which Su(Hw) promotes proper oogenesis remains unclear. To gain insight into the functional properties of chromatin insulators, we further characterize the oogenesis phenotypes of su(Hw) mutant females. We find that mutant egg chambers frequently display an irregular number of nurse cells, have poorly formed microtubule organization centers (MTOC) in the germarium, and show mislocalized Gurken (Grk) in later stages of oogenesis. Furthermore, eggshells produced by partially rescued su(Hw) mutant females exhibit dorsoventral patterning defects that are identical to defects found in spindle mutants or in piRNA pathway mutants. Further analysis reveals an excess of DNA damage in egg chambers, which is independent of activation of transposable elements, and that Gurken localization defects and oogenesis progression are partially rescued by mutations in mei-41 and chk1 genes. In addition, we show that Su(Hw) is required for chromosome integrity in dividing neuroblasts from larval brains. Together, these findings suggest that Su(Hw) plays a critical role in maintaining genome integrity during germline development in Drosophila females as well as in dividing somatic cells.