Sen1 and Rrm3 ensure permissive topological conditions for replication termination

• Published in: Cell reports (Cambridge) 2023-07, Vol.42 (7), p.112747-112747, Article 112747
• Main Authors: Choudhary, Ramveer, Niska-Blakie, Joanna, Adhil, Mohamood, Liberi, Giordano, Achar, Yathish Jagadheesh, Giannattasio, Michele, Foiani, Marco
• Format: Article
• Language: English
• Subjects: CP: Molecular biology; DNA; DNA Helicases - genetics; DNA Helicases - metabolism; DNA Replication; DNA Topoisomerases, Type II - metabolism; DNA topology; replication termination; RNA Helicases - genetics; RNA Helicases - metabolism; RNPII; Rrm3; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Senataxin; telomeres; Top1; Top2
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112747

Replication forks terminate at TERs and telomeres. Forks that converge or encounter transcription generate topological stress. Combining genetics, genomics, and transmission electron microscopy, we find that Rrm3hPif1 and Sen1hSenataxin helicases assist termination at TERs; Sen1 specifically acts at telomeres. rrm3 and sen1 genetically interact and fail to terminate replication, exhibiting fragility at termination zones (TERs) and telomeres. sen1rrm3 accumulates RNA-DNA hybrids and X-shaped gapped or reversed converging forks at TERs; sen1, but not rrm3, builds up RNA polymerase II (RNPII) at TERs and telomeres. Rrm3 and Sen1 restrain Top1 and Top2 activities, preventing toxic accumulation of positive supercoil at TERs and telomeres. We suggest that Rrm3 and Sen1 coordinate the activities of Top1 and Top2 when forks encounter transcription head on or codirectionally, respectively, thus preventing the slowing down of DNA and RNA polymerases. Hence Rrm3 and Sen1 are indispensable to generate permissive topological conditions for replication termination. [Display omitted] •Rrm3 and Sen1 assist replication termination•Rrm3 and Sen1 restrain Top1 and Top2 at TERs and telomeres•Rrm3 and Sen1 helicases prevent aberrant topological events at TERs•Positive supercoiling accumulation induces fork reversal at TERs Replicon fusion is topologically challenging. Replication termination occurs at TER zones and telomeres. Choudhary et al. show that replication termination is assisted by transcription and by Sen1 and Rrm3 helicases that coordinate the activities of Top1 and Top2 topoisomerases at TERs and telomeres.