Fraser Andrew
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Oncogene. 2004 Nov 1;23(51):8346-52. doi: 10.1038/sj.onc.1208044.
Cancer is a genetic disease that ultimately results from the failure of cells to respond correctly to diverse signals. Signal transduction and signal integration are highly complex, requiring the combinatorial interaction of multiple genes. Classical genetics in model organisms including Caenorhabditis elegans has been of immense use in identifying nonredundant components of conserved signalling pathways. However, it is likely that there is much functional redundancy in the informational processing machinery of metazoan cells; we therefore need to develop methods for uncovering such redundant functions in model organisms if we are to use them to understand complex gene interactions and oncogene cooperation. RNAi may provide a powerful tool to probe redundancy in informational networks. In this review, I set out some of the progress made so far by classical genetics in understanding redundancy in gene networks, and outline how RNAi may allow us to approach this problem more systematically in C. elegans. In particular, I discuss the use of genome-wide RNAi screens in C. elegans to identify synthetic lethal interactions and compare this with synthetic lethal interaction analysis in Saccharomyces cerevisiae.
癌症是一种遗传性疾病，最终源于细胞无法正确响应各种信号。信号转导和信号整合高度复杂，需要多个基因的组合相互作用。包括秀丽隐杆线虫在内的模式生物中的经典遗传学在识别保守信号通路的非冗余成分方面发挥了巨大作用。然而，后生动物细胞的信息处理机制中很可能存在大量功能冗余；因此，如果我们要用模式生物来理解复杂的基因相互作用和癌基因协同作用，就需要开发方法来揭示这些模式生物中的冗余功能。RNA干扰可能提供一个强大的工具来探究信息网络中的冗余性。在这篇综述中，我阐述了经典遗传学目前在理解基因网络冗余性方面取得的一些进展，并概述了RNA干扰如何使我们能够在秀丽隐杆线虫中更系统地解决这个问题。特别是，我讨论了在秀丽隐杆线虫中使用全基因组RNA干扰筛选来识别合成致死相互作用，并将其与酿酒酵母中的合成致死相互作用分析进行比较。
