Participants in Transcription–Replication Conflict and Their Role in Formation and Resolution of R-Loops

The DNA of all living organisms is a common matrix for both replication and transcription processes. This sometimes leads to inevitable collisions between DNA replication and transcription machinery. There is plethora of evidence demonstrating that such collisions (or TRCs) are one of the most common and significant reasons for genomic instability. One of the key outcomes of TRCs is the accumulation of non-canonical DNA secondary structures, including R-loops. R-loops are three-stranded DNA-RNA hybrids with a displaced third single-stranded DNA fragment. Although R-loops are thought to play several functional roles in biological processes, an imbalance in their metabolism has been proven to have severe consequences. In this review, we attempt to summarize the current knowledge of the participants in the process of R-loop regulation in cells, with an emphasis on eukaryotic systems. We also touch upon the conditions favoring TRCs and the possible ways of dealing with these conflicts.