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

正确执行胚胎发育依赖于生物体适应压力的能力。在早期阶段的果蝇胚胎中，核沉降的过程使得能够在中囊胚过渡期间选择性地消除具有复制缺陷或过度DNA损伤的细胞核。控制核沉降的分子机制长期以来一直知之甚少。在最近的一项研究中，我们的研究小组定义了一种新的机制，通过这种机制，Chk2激酶介导的DNA损伤信号传导导致转录的mRNA选择性保留在沉降核中，阻止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），组蛋白mRNA核输出所需的RNA结合蛋白（RBP），作为直接靶点Chk2。虽然SLBP是解释组蛋白mRNA在沉降核中的核保留的关键目标，但其他几种mRNA通过SLBP独立机制保留。因此我们