Distinct mechanisms of replication stress induced by oncogenic RAS and cyclin E1 converge on R-loop-dependent fork reversal - PubMed
21 hours ago
- #R-loops
- #Oncogenic Signaling
- #Replication Stress
- Oncogenic RAS (HRASV12) and cyclin E1 overexpression induce replication stress, primarily via R-loops during S-phase.
- HRASV12-induced replication stress is ROS-dependent, mediated by the ROS sensor PRDX2 and linked to TIMELESS release.
- Fork reversal inhibition in HRASV12 or cyclin E1 cells leads to MUS81- and PRIMPOL-mediated DNA synthesis, aiding chromosome segregation.
- PRIMPOL repriming is part of a MUS81-dependent restart mechanism for R-loop-mediated conflicts to maintain genomic stability.
- Persistent reversed forks can impair mitosis, causing DNA breaks and chromosomal rearrangements despite protective roles in S-phase.