Transcript profiling of WT and lsm1∆ Saccharomyces cells before and after 1, 2 and 4 hours of hydroxyurea treatment (200 mM)

mRNA processing bodies (P-bodies) are cytoplasmic granules that form in eukaryotic cells in response to numerous stresses to serve as sites of degradation and storage of mRNAs. Functional P-bodies are critical for the DNA replication stress response in yeast, yet the repertoire of P-body targets and the mechanisms by which P-bodies promote replication stress resistance are unknown. In this study, we identify the complete complement of mRNA targets of P-bodies during replication stress induced by hydroxyurea treatment. The key P-body protein Lsm1 controls the abundance of HHT1, ACF4, ARL3, TMA16, RRS1 and YOX1 mRNAs to prevent their toxic accumulation during replication stress. Accumulation of YOX1 mRNA causes aberrant down-regulation of a network of genes critical for DNA replication stress resistance. Among these genes we identify ALD6, whose de-repression is critical to prevent accumulation of acetaldehyde, a strongly toxic molecule during DNA replication stress.mRNA加工小体（mRNA processing bodies，P-bodies）是真核细胞响应多种应激后形成的胞质颗粒，可作为mRNA降解与储存的位点。具有功能的P-bodies在酵母的DNA复制应激反应中发挥关键作用，但目前尚不明确P-body的靶标谱，以及P-bodies促进复制应激抗性的具体分子机制。本研究鉴定了羟基脲诱导的复制应激状态下，P-bodies的全部mRNA靶标。关键P-body蛋白Lsm1可调控HHT1、ACF4、ARL3、TMA16、RRS1及YOX1的mRNA丰度，以防止这些mRNA在复制应激过程中发生毒性积累。YOX1 mRNA的积累会导致一批对DNA复制应激抗性至关重要的基因调控网络发生异常下调。在这些基因中，我们鉴定出ALD6；其去抑制作用对于阻止乙醛——一种在DNA复制应激过程中具有强毒性的小分子——的积累至关重要。