Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla, 41092 Seville, Spain.
Cold Spring Harb Perspect Biol. 2014 Aug 1;6(8):a016543. doi: 10.1101/cshperspect.a016543.
A particularly relevant phenomenon in cell physiology and proliferation is the fact that spontaneous mitotic recombination is strongly enhanced by transcription. The most accepted view is that transcription increases the occurrence of double-strand breaks and/or single-stranded DNA gaps that are repaired by recombination. Most breaks would arise as a consequence of the impact that transcription has on replication fork progression, provoking its stalling and/or breakage. Here, we discuss the mechanisms responsible for the cross talk between transcription and recombination, with emphasis on (1) the transcription-replication conflicts as the main source of recombinogenic DNA breaks, and (2) the formation of cotranscriptional R-loops as a major cause of such breaks. The new emerging questions and perspectives are discussed on the basis of the interference between transcription and replication, as well as the way RNA influences genome dynamics.
细胞生理学和增殖中一个特别相关的现象是,转录强烈促进自发有丝分裂重组。最被接受的观点是,转录增加了双链断裂和/或单链 DNA 缺口的发生,这些断裂通过重组来修复。大多数断裂是由于转录对复制叉进展的影响而产生的,导致其停滞和/或断裂。在这里,我们讨论了转录和重组之间相互作用的机制,重点是 (1) 转录-复制冲突作为产生重组 DNA 断裂的主要来源,以及 (2) 共转录 R-环的形成作为这种断裂的主要原因。基于转录和复制之间的干扰以及 RNA 影响基因组动力学的方式,讨论了新出现的问题和观点。