Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response
Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response
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DOI：
10.1016/j.devcel.2006.12.001
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发表时间：
2007-01-01
影响因子：
11.8
通讯作者：
Theurkauf, William E.
中科院分区：
文献类型：
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作者：
Klattenhoff, Carla;Bratu, Diana P.;Theurkauf, William E.
小重复序列相关siRNAs(RasiRNAs)介导逆转录转座子和星状基因的沉默。果蝇rsiRNA途径基因Armitage和Aubergine的突变扰乱了胚轴的指定，引发了微管极化的缺陷以及发育中的卵母细胞中mRNA和蛋白质决定因素的不对称定位。ATR/Chk2 DNA损伤信号转导通路中的突变极大地抑制了这些轴指定缺陷，但不能恢复反转录转座子或星状沉默。此外，rasiRNA途径突变导致种系特异性地积累具有DNA损伤特征的伽马-H_2Av焦点。我们得出结论，基于rasiRNA的基因沉默不是AXIS指定所必需的，这一途径的关键发育功能是抑制生殖系中的DNA损伤信号。
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.