Transcription-replication conflicts at chromosomal fragile sites-consequences in M phase and beyond.

Collision between the molecular machineries responsible for transcription and replication is an important source of genome instability. Certain transcribed regions known as chromosomal fragile sites are particularly prone to recombine and mutate in a manner that correlates with specific transcription and replication patterns. At the same time, these chromosomal fragile sites engage in aberrant DNA structures in mitosis. Here, we discuss the mechanistic details of transcription-replication conflicts including putative scenarios for R-loop-induced replication inhibition to understand how transcription-replication conflicts transition from S phase into various aberrant DNA structures in mitosis.