Mutations in the insulator protein Suppressor of Hairy wing induce genome instability View Full Text


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Article Info

DATE

2020-11-02

AUTHORS

Shih-Jui Hsu, Emily C. Stow, James R. Simmons, Heather A. Wallace, Andrea Mancheno Lopez, Shannon Stroud, Mariano Labrador

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. More... »

PAGES

255-274

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00412-020-00743-8

    DOI

    http://dx.doi.org/10.1007/s00412-020-00743-8

    DIMENSIONS

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    33 schema:description 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.
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    41 Chk1 (grapes) DNA damage response genes
    42 DNA damage
    43 DNA damage response genes
    44 Drosophila
    45 Drosophila development
    46 Drosophila insulator proteins
    47 Gurken localization defects
    48 Hairy wing
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    50 anterior/posterior axis specification factor
    51 axis specification factor
    52 brain
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    55 cells
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    57 chamber
    58 chromosome breaks
    59 class
    60 communication
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    72 factors
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    83 genome integrity
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    86 germ cells
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    90 important class
    91 important functions
    92 instability
    93 insulator
    94 insulator protein Suppressor
    95 insulator proteins
    96 integrity
    97 larval brain
    98 later oogenesis stages
    99 localization defects
    100 maintenance
    101 microtubule organization center
    102 mislocalization
    103 mutant female germline exhibit dorsoventral patterning defects
    104 mutants
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    107 number
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    109 oogenesis
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    111 organization
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    115 phenotype
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    118 posterior axis specification factor
    119 promoter
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    122 regulation
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