Drosophila rasiRNA Pathway Mutations Disrupt Embryonic Axis Specification through Activation of an ATR/Chk2 DNA Damage Response

Program in Molecular Medicine and Program in Cell Dynamics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Developmental Cell (Impact Factor: 9.71). 02/2007; 12(1):45-55. DOI: 10.1016/j.devcel.2006.12.001
Source: PubMed


Small repeat-associated siRNAs (rasiRNAs) mediate silencing of retrotransposons and the Stellate locus. Mutations in the Drosophila rasiRNA pathway genes armitage and aubergine disrupt embryonic axis specification, triggering defects in microtubule polarization as well as asymmetric localization of mRNA and protein determinants in the developing oocyte. Mutations in the ATR/Chk2 DNA damage signal transduction pathway dramatically suppress these axis specification defects, but do not restore retrotransposon or Stellate silencing. Furthermore, rasiRNA pathway mutations lead to germline-specific accumulation of gamma-H2Av foci characteristic of DNA damage. We conclude that rasiRNA-based gene silencing is not required for axis specification, and that the critical developmental function for this pathway is to suppress DNA damage signaling in the germline.

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    • "In the absence of piRNAs, TEs become expressed and induce various oogenesis defects (early arrest of egg chamber development, dorsoventral patterning defects, etc.) leading to sterility. Interestingly , these phenotypes are due to the activation of DNA damage checkpoint proteins of the ATR/Chk2 pathway (Chen et al, 2007; Klattenhoff et al, 2007; Pane et al, 2007). Indeed, inactivating chk2 in piRNA mutants such as aubergine (aub) or armitage (armi) rescues most of the morphological defects during oogenesis. "
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    • "In animals, PIWI-interacting RNAs (piRNAs), a diverse class of 23À36 nucleotide (nt) small silencing RNAs, repress transposons in the germline, ensuring the faithful transfer of genomic information from generation to generation (Girard et al., 2006; Aravin et al., 2006; Grivna et al., 2006; Lau et al., 2006; Vagin et al., 2006). Disrupting the piRNA pathway activates transposon transcription , arresting germ cell development (Wilson et al., 1996; Lin and Spradling, 1997; Deng and Lin, 2002; Klattenhoff et al., 2007) and making one or both sexes infertile. Drosophila germline nurse cells produce piRNAs by at least two mechanisms: the de novo pathway and the ping-pong cycle. "
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