Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, E-08003 Barcelona, Spain.
J Mol Biol. 2013 Nov 29;425(23):4745-55. doi: 10.1016/j.jmb.2013.08.019. Epub 2013 Sep 7.
Transcription during S phase needs to be spatially and temporally regulated to prevent collisions between the transcription and replication machineries. Cells have evolved a number of mechanisms to make both processes compatible under normal growth conditions. When conflict management fails, the head-on encounter between RNA and DNA polymerases results in genomic instability unless conflict resolution mechanisms are activated. Nevertheless, there are specific situations in which cells need to dramatically change their transcriptional landscape to adapt to environmental challenges. Signal transduction pathways, such as stress-activated protein kinases (SAPKs), serve to regulate gene expression in response to environmental insults. Prototypical members of SAPKs are the yeast Hog1 and mammalian p38. In response to stress, p38/Hog1 SAPKs control transcription and also regulate cell cycle progression. When yeast cells are stressed during S phase, Hog1 promotes gene induction and, remarkably, also delays replication by directly affecting early origin firing and fork progression. Therefore, by delaying replication, Hog1 plays a key role in preventing conflicts between RNA and DNA polymerases. In this review, we focus on the genomic determinants and mechanisms that make compatible transcription with replication during S phase to prevent genomic instability, especially in response to environmental changes.
在 S 期，转录需要在空间和时间上进行调节，以防止转录和复制机制之间发生碰撞。细胞已经进化出许多机制，使这两个过程在正常生长条件下兼容。当冲突管理失败时，RNA 和 DNA 聚合酶之间的正面碰撞会导致基因组不稳定，除非激活冲突解决机制。然而，在某些特定情况下，细胞需要大幅改变其转录景观以适应环境挑战。信号转导途径，如应激激活蛋白激酶 (SAPKs)，用于调节基因表达以响应环境损伤。SAPKs 的典型成员是酵母 Hog1 和哺乳动物 p38。当酵母细胞在 S 期受到应激时，p38/Hog1 SAPKs 控制转录，并且还通过直接影响早期起始点火和叉进展来调节细胞周期进程。因此，通过延迟复制，Hog1 在防止 RNA 和 DNA 聚合酶之间发生冲突方面发挥着关键作用。在这篇综述中，我们重点介绍了在 S 期使转录与复制兼容的基因组决定因素和机制，以防止基因组不稳定，特别是在响应环境变化时。
