果蝇rasiRNA通路突变通过激活ATR/Chk2 DNA损伤反应破坏胚胎轴的指定。

Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response.

作者信息

Klattenhoff Carla, Bratu Diana P, McGinnis-Schultz Nadine, Koppetsch Birgit S, Cook Heather A, Theurkauf William E

机构信息

Program in Molecular Medicine and Program in Cell Dynamics, University of Massachusetts Medical School, Worcester, MA 01605, USA.

出版信息

Dev Cell. 2007 Jan;12(1):45-55. doi: 10.1016/j.devcel.2006.12.001.

DOI:10.1016/j.devcel.2006.12.001

PMID:17199040

Abstract

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.

摘要

小重复相关小干扰RNA（rasiRNA）介导逆转座子和星状体基因座的沉默。果蝇rasiRNA途径基因阿米蒂奇（Armitage）和茄子（Aubergine）的突变会破坏胚胎轴的指定，引发微管极化缺陷以及发育中卵母细胞中mRNA和蛋白质决定簇的不对称定位。ATR/Chk2 DNA损伤信号转导途径中的突变可显著抑制这些轴指定缺陷，但不能恢复逆转座子或星状体的沉默。此外，rasiRNA途径突变会导致生殖系特异性积累DNA损伤特征性的γ-H2Av焦点。我们得出结论，基于rasiRNA的基因沉默对于轴指定不是必需的，并且该途径的关键发育功能是抑制生殖系中的DNA损伤信号。