Molecular and Cellular Biology Graduate Program and Medical Scientist Training Program, University of Washington, Seattle, WA, USA.
Department of Biochemistry, Vanderbilt University, Nashville, TN, 37205, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
DNA Repair (Amst). 2019 Sep;81:102659. doi: 10.1016/j.dnarep.2019.102659. Epub 2019 Jul 8.
Conflicts between replication and transcription can have life-threatening consequences. RNA polymerase (RNAP) is the major impediment to replication progression, and its efficient removal from DNA should mitigate the consequences of collisions with replication. Cells have various proteins that can resolve conflicts by removing stalled (or actively translocating) RNAP from DNA. It would therefore seem logical that RNAP-associated factors, such as the bacterial DNA translocase Mfd, would minimize the effects of conflicts. Despite seemingly conclusive statements in most textbooks, the role of Mfd in conflicts remains an enigma. In this review, we will discuss the different physical states of RNAP during transcription, and how each distinct state can influence conflict severity and potentially trigger the involvement of Mfd. We propose models to explain the contradictory conclusions from published studies on the potential role of Mfd in resolving conflicts.
复制和转录之间的冲突可能会带来危及生命的后果。RNA 聚合酶(RNAP)是复制进程的主要障碍,其从 DNA 中有效去除应减轻与复制碰撞的后果。细胞具有多种蛋白质,可以通过将停滞(或主动转运)的 RNAP 从 DNA 上移除来解决冲突。因此,RNAP 相关因子(如细菌 DNA 转位酶 Mfd)似乎可以最小化冲突的影响,这似乎是合乎逻辑的。尽管大多数教科书中都有看似确凿的陈述,但 Mfd 在冲突中的作用仍然是一个谜。在这篇综述中,我们将讨论转录过程中 RNAP 的不同物理状态,以及每种不同状态如何影响冲突的严重程度,并可能触发 Mfd 的参与。我们提出了一些模型来解释发表的研究中关于 Mfd 在解决冲突方面的潜在作用的相互矛盾的结论。