Mutations in the insulator protein Suppressor of Hairy wing induce genome instability
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ORIGINAL ARTICLE
Mutations in the insulator protein Suppressor of Hairy wing induce genome instability Shih-Jui Hsu 1 & Emily C. Stow 1 & James R. Simmons 1 & Heather A. Wallace 1 & Andrea Mancheno Lopez 1 & Shannon Stroud 1 & Mariano Labrador 1 Received: 9 July 2020 / Revised: 21 October 2020 / Accepted: 22 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Insulator proteins orchestrate the three-dimensional organization of the genome. Insulators function by facilitating communications between regulatory sequences and gene promoters, allowing accurate gene transcription regulation during embryo development and cell differentiation. However, the role of insulator proteins beyond genome organization and transcription regulation remains unclear. Suppressor of Hairy wing [Su(Hw)] is a Drosophila insulator protein that plays an important function in female oogenesis. Here we find that su(Hw) has an unsuspected role in genome stability during cell differentiation. We show that su(Hw) mutant developing egg chambers have poorly formed microtubule organization centers (MTOCs) in the germarium and display mislocalization of the anterior/ posterior axis specification factor gurken in later oogenesis stages. Additionally, eggshells from partially rescued su(Hw) mutant female germline exhibit dorsoventral patterning defects. These phenotypes are very similar to phenotypes found in the important class of spindle mutants or in piRNA pathway mutants in Drosophila, in which defects generally result from the failure of germ cells to repair DNA damage. Similarities between mutations in su(Hw) and spindle and piRNA mutants are further supported by an excess of DNA damage in nurse cells, and because Gurken localization defects are partially rescued by mutations in the ATR (mei-41) and Chk1 (grapes) DNA damage response genes. Finally, we also show that su(Hw) mutants produce an elevated number of chromosome breaks in dividing neuroblasts from larval brains. Together, these findings suggest that Su(Hw) is necessary for the maintenance of genome integrity during Drosophila development, in both germline and dividing somatic cells. Keywords Chromatin insulators . Suppressor of hairy wing (Su(Hw)) . Drosophila . DNA damage response . Replication stress
Introduction Chromatin insulators facilitate higher-order chromatin organization in the nucleus by mediating mechanisms that promote Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s00412-02000743-8. * Mariano Labrador [email protected] 1
Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, TN 37996, USA
2
Present address: Department of Cancer Biology, University of Cincinnati, Cincinnati, OH 45267, USA
3
Present address: Department of Structural and Cellular Biology, Tulane University, New Orleans, LA 70112, USA
4
Present address: Massachusetts General Hospital, Richard B. Simches Research Center, 185 Cambridge Street, Boston, MA 02114,
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