Article abstract
Nature Structural & Molecular Biology 15, 722 - 729 (2008)
Published online: 8 June 2008 | doi:10.1038/nsmb.1439
Asymmetric bidirectional replication at the human DBF4 origin
Julia Romero1,2 & Hoyun Lee1,2,3
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'.
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
- Tumour Biology Group, Northeastern Ontario Regional Cancer Centre, Sudbury Regional Hospital, 41 Ramsey Lake Road, Sudbury, Ontario P3E 5J1, Canada.
- Department of Medical Sciences, the Northern Ontario School of Medicine, 935 Ramsey Lake Road, Sudbury, Ontario P3E 2C6, Canada.
Correspondence to: Hoyun Lee1,2,3 e-mail: hlee@hrsrh.on.ca
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