A large body of research supports that transcription plays a major role among the many sources of replicative stress contributing to genome instability. It is therefore not surprising that the DNA damage response has a role in the prevention of transcription-induced threatening events such as the formation of DNA-RNA hybrids, as we have recently found through an siRNA screening. Three major DDR pathways were defined to participate in the protection against DNA-RNA hybrids: ATM/CHK2, ATR/CHK1 and Postreplication Repair (PRR). Based on these observations, we envision different scenarios of DNA-RNA hybridization and their consequent DNA damage.
Keywords: DNA damage response; DNA-RNA hybrids; genetic instability; postreplication repair; replicative stress.