biostudies-literatureUruci SSwiss National Science FoundationEuropean Research Council1025-1034https://www.ebi.ac.uk/biostudies/studies/S-EPMC12935552biostudies-literatureUnknown650(8103)Fine-tuning DNA replication and transcription is crucial to prevent collisions between their machineries¹. This is particularly important near promoters, where RNA polymerase II (RNAPII) initiates transcription and frequently arrests, forming R-loops^2-4. Arrested RNAPII can obstruct DNA replication, which often initiates near promoters^5,6. The mechanisms that rescue arrested RNAPII during elongation to avoid conflicts with co-directional replisomes remain unclear. Here, using genome-wide approaches and genetic screens, we identify CFAP20 as part of a protective pathway that salvages arrested RNAPII in promoter-proximal regions, diverting it from the path of co-directional replisomes. CFAP20-deficient cells accumulate R-loops near promoters, which leads to dNatureCFAP20 salvages arrested RNAPII from the path of co-directional replisomes.PMC12935552852798310913101053581197003101043815Wendel TJTropepe Vde Lint KPanagopoulos AWolthuis RMFBoer DECvan Attikum HWondergem APVertegaal ACOKirdok IAltmeyer Mvan Oudenaarden ALingeman JLjungman Mvan den Heuvel DUruci SBrussee SJHamperl SLalonde MYakoub GChrystal PWNoordermeer SMLuijsterburg MSvan den Berg Jvan der Woude Mvan Overbeek NKSchotman NfalseCFAP20 salvages arrested RNAPII from the path of co-directional replisomes.Fine-tuning DNA replication and transcription is crucial to prevent collisions between their machineries¹. This is particularly important near promoters, where RNA polymerase II (RNAPII) initiates transcription and frequently arrests, forming R-loops^2-4. Arrested RNAPII can obstruct DNA replication, which often initiates near promoters^5,6. The mechanisms that rescue arrested RNAPII during elongation to avoid conflicts with co-directional replisomes remain unclear. Here, using genome-wide approaches and genetic screens, we identify CFAP20 as part of a protective pathway that salvages arrested RNAPII in promoter-proximal regions, diverting it from the path of co-directional replisomes. CFAP20-deficient cells accumulate R-loops near promoters, which leads to d2026-01-01T00:00:00Z2026 Feb2026-07-16T21:56:54.676Z2026-07-10T03:15:56.349ZS-EPMC129355524153546110.1038/s41586-025-09943-7