During S phase, the replisome has to overcome many physical obstacles that can 
cause replication fork stalling and compromise genome integrity. Transcription 
is an important source of replicative stress and consequently, maintenance of 
genome integrity requires the protection of chromosomes from the deleterious 
effects arising from the interaction between nascent RNAs and template DNA, 
leading to stable DNA-RNA hybrids (R-loop) formation. We previously reported the 
essential role of Omcg1 (Ovum Mutant Candidate Gene) for cell cycle progression 
during early embryonic development. Here, we show that OMCG1 is a target of the 
cell cycle checkpoint kinases ATR/ATM and is essential for S phase progression 
in mouse embryonic fibroblasts. Using a conditional gene inactivation strategy, 
we demonstrate that OMCG1 depletion impairs cell viability as a consequence of 
DSB formation, checkpoint activation and replication fork collapse. We also show 
that no chromosome breaks were generated in non-cycling Omcg1-deficient cells. 
Furthermore, increased RNaseH expression significantly alleviated genomic 
instability in deficient fibroblasts suggesting that cotranscriptional R-loops 
formation contributes to the genesis of replication-dependent DSBs in these 
cells. Together with recent reports describing its participation to complexes 
involved in cotanscriptional processes, our results suggest that OMCG1 plays a 
role in the tight coupling between mRNA processing pathways and maintenance of 
genome integrity during cell cycle progression.