Pan Xuewen, Ye Ping, Yuan Daniel S, Wang Xiaoling, Bader Joel S, Boeke Jef D
Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.
Cell. 2006 Mar 10;124(5):1069-81. doi: 10.1016/j.cell.2005.12.036. Epub 2006 Feb 16.
A network governing DNA integrity was identified in yeast by a global genetic analysis of synthetic fitness or lethality defect (SFL) interactions. Within this network, 16 functional modules or minipathways were defined based on patterns of global SFL interactions. Modules or genes involved in DNA replication, DNA-replication checkpoint (DRC) signaling, and oxidative stress response were identified as the major guardians against lethal spontaneous DNA damage, efficient repair of which requires the functions of the DNA-damage checkpoint signaling and multiple DNA-repair pathways. This genome-wide genetic interaction network also identified novel components (DIA2, NPT1, HST3, HST4, and the CSM1 module) that potentially contribute to mitotic DNA replication and genomic stability and revealed novel functions of well-studied genes (the CTF18 module) in DRC signaling. This network will guide more detailed characterization of mechanisms governing DNA integrity in yeast and other organisms.
通过对合成适应性或致死缺陷（SFL）相互作用进行全面的遗传分析，在酵母中鉴定出了一个调控DNA完整性的网络。在这个网络中，基于全面的SFL相互作用模式定义了16个功能模块或小通路。参与DNA复制、DNA复制检查点（DRC）信号传导和氧化应激反应的模块或基因被确定为防止致死性自发DNA损伤的主要守护者，而其有效修复需要DNA损伤检查点信号传导和多种DNA修复途径的功能。这个全基因组遗传相互作用网络还鉴定出了可能有助于有丝分裂DNA复制和基因组稳定性的新成分（DIA2、NPT1、HST3、HST4和CSM1模块），并揭示了在DRC信号传导中研究充分的基因（CTF18模块）的新功能。该网络将指导对酵母和其他生物体中调控DNA完整性机制的更详细表征。
