Abstract
Faithful replication of the entire genome once per cell cycle is essential for maintaining genetic integrity, and the origin of DNA replication is key in this regulation. Unlike that in unicellular organisms, the replication initiation mechanism in mammalian cells is not well understood. We have identified a strong origin of replication at the DBF4 promoter locus, which contains two initiation zones, two origin recognition complex (ORC) binding sites and two DNase I–hypersensitive regions within ∼1.5 kb. Notably, similar to the Escherichia coli oriC, replication at the DBF4 locus starts from initiation zone I, which contains an ORC-binding site, and progresses in the direction of transcription toward initiation zone II, located ∼0.4 kb downstream. Replication on the opposite strand from zone II, which contains another ORC-binding site, may be activated or facilitated by replication from zone I. We term this new mammalian replication mode 'asymmetric bidirectional replication'.
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Acknowledgements
We are grateful to S.-Y. Kim for her initial development of the ChIP assay protocol. This work was supported by grants from the Canadian Institutes of Health Research (MOP79473) to H.L. J.R. was supported in part by a graduate scholarship of the University of Ottawa.
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J.R. planned, developed protocols, carried out experiments, analyzed data and drafted the manuscript; H.L. conceived and guided the overall research project, analyzed and interpreted data, and wrote the final version of the manuscript.
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Romero, J., Lee, H. Asymmetric bidirectional replication at the human DBF4 origin. Nat Struct Mol Biol 15, 722–729 (2008). https://doi.org/10.1038/nsmb.1439
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DOI: https://doi.org/10.1038/nsmb.1439
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