DNA Damage Signaling and Transcriptome Regulation in Drosophila Embryogenesis

果蝇胚胎发生中的 DNA 损伤信号转导和转录组调控

• 批准号: RGPIN-2017-04614
• 负责人: Lecuyer, Eric
• 金额: $ 2.91万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629588
• 关键词: DNA; Damage; Signaling; Transcriptome; Regulation

: The faithful execution of embryonic development relies on the capacity of organisms to adapt to stress. In early stage Drosophila embryos, a process of nuclear fallout enables the selective elimination of nuclei with replication defects or excessive DNA damage during the midblastula transition. The molecular mechanisms controlling nuclear fallout have long remained poorly understood. In a recent study, our group defined a novel mechanism through which DNA-damage signalling mediated by the Chk2 kinase leads to the selective retention of transcribed mRNAs in fallout nuclei, blocking the translation of transcripts encoding key proteins. Our work identified the stem loop binding protein (SLBP), an RNA binding protein (RBP) required for histone mRNA nuclear export, as a direct target Chk2. While SLBP is a key target explaining histone mRNA nuclear retention in fallout nuclei, several other mRNAs are retained through SLBP-independent mechanisms. Thus, we

：胚胎发育的忠实执行依赖于生物体适应压力的能力。在果蝇胚胎的早期阶段，核沉降过程能够选择性地消除在囊胚转变期间复制缺陷或过度 DNA 损伤的细胞核。长期以来，人们对控制核尘埃的分子机制仍知之甚少。在最近的一项研究中，我们的小组定义了一种新机制，通过该机制，由 Chk2 激酶介导的 DNA 损伤信号传导导致转录 mRNA 选择性保留在沉降核中，从而阻断编码关键蛋白的转录本的翻译。我们的工作确定了茎环结合蛋白 (SLBP)，一种组蛋白 mRNA 核输出所需的 RNA 结合蛋白 (RBP)，作为 Chk2 的直接靶标。虽然 SLBP 是解释组蛋白 mRNA 保留在沉降核中的关键靶标，但其他几种 mRNA 通过 SLBP 独立机制保留。因此，我们