FORK-seq: replication landscape of the Saccharomyces cerevisiae genome by nanopore sequencing

Hennion, M.; Arbona, J.-M.; Lacroix, L.; Cruaud, C.; Theulot, B.; Le Tallec, B.; Proux, F.; Wu, X.; Novikova, E.; Engelen, S.; Lemainque, A.; Audit, B.; Hyrien, O.

doi:10.1101/2020.04.09.033720

bioRxiv · 10.1101/2020.04.09.033720

FORK-seq: replication landscape of the Saccharomyces cerevisiae genome by nanopore sequencing

Hennion, M.·Arbona, J.-M.·Lacroix, L.·Cruaud, C.·Theulot, B.·Le Tallec, B.·Proux, F.·Wu, X.·Novikova, E.·Engelen, S.·Lemainque, A.·Audit, B.·Hyrien, O.

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Abstract

Genome replication mapping methods profile cell populations, masking cell-to-cell heterogeneity. Here, we describe FORK-seq, a nanopore sequencing method to map replication of single DNA molecules at 200 nucleotide resolution. By quantifying BrdU incorporation along pulse-chased replication intermediates from Saccharomyces cerevisiae, we orient 58,651 replication tracks reproducing population-based replication directionality profiles and map 4,964 and 4,485 individual initiation and termination events, respectively. Although most events cluster at known origins and fork merging zones, 9% and 18% of initiation and termination events, respectively, occur at many locations previously missed. Thus, FORK-seq reveals the full extent of cell-to-cell heterogeneity in DNA replication.

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Hennion, M., Arbona, J.-M., Lacroix, L., Cruaud, C., Theulot, B., Le Tallec, B., Proux, F., Wu, X., Novikova, E., Engelen, S., Lemainque, A., Audit, B., Hyrien, O.. 2020-04-10. FORK-seq: replication landscape of the Saccharomyces cerevisiae genome by nanopore sequencing. https://doi.org/10.1101/2020.04.09.033720

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