Cooke Matthew B, Herman Christophe, Sivaramakrishnan Priya
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
FEBS Lett. 2025 Jan;599(2):209-243. doi: 10.1002/1873-3468.15063. Epub 2024 Nov 24.
DNA replication and RNA transcription processes compete for the same DNA template and, thus, frequently collide. These transcription-replication collisions are thought to lead to genomic instability, which places a selective pressure on organisms to avoid them. Here, we review the predisposing causes, molecular mechanisms, and downstream consequences of transcription-replication collisions (TRCs) with a strong emphasis on prokaryotic model systems, before contrasting prokaryotic findings with cases in eukaryotic systems. Current research points to genomic structure as the primary determinant of steady-state TRC levels and RNA polymerase regulation as the primary inducer of excess TRCs. We review the proposed mechanisms of TRC-induced DNA damage, attempting to clarify their mechanistic requirements. Finally, we discuss what drives genomes to select against TRCs.
DNA复制和RNA转录过程会竞争相同的DNA模板，因此经常发生碰撞。这些转录-复制碰撞被认为会导致基因组不稳定，这对生物体形成了避免此类碰撞的选择压力。在此，我们着重围绕原核生物模型系统，综述转录-复制碰撞（TRCs）的诱发原因、分子机制及下游后果，然后将原核生物的研究结果与真核生物系统中的情况进行对比。当前研究表明，基因组结构是稳态TRC水平的主要决定因素，而RNA聚合酶调控是过量TRCs的主要诱导因素。我们综述了TRC诱导DNA损伤的推测机制，试图阐明其机制要求。最后，我们讨论是什么促使基因组选择避免TRCs。
