Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 19, Issue 8, Pages 837-844Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2339
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Funding
- AVENIR INSERM program
- associated INCa support [Convention 2007/3D1616/InsermAvenir-22-1/NG-NC]
- Ministere de l'Education Nationale, de la Recherche et de is Technologie
- Fondation pour la Recherche Medicale [DCR20091217183]
- Association pour la Recherche contre le Cancer
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DNA replication is highly regulated, ensuring faithful inheritance of genetic information through each cell cycle. In metazoans, this process is initiated at many thousands of DNA replication origins whose cell type-specific distribution and usage are poorly understood. We exhaustively mapped the genome-wide location of replication origins in human cells using deep sequencing of short nascent strands and identified ten times more origin positions than we expected; most of these positions were conserved in four different human cell lines. Furthermore, we identified a consensus G-quadruplex-forming DNA motif that can predict the position of DNA replication origins in human cells, accounting for their distribution, usage efficiency and timing. Finally, we discovered a cell type-specific reprogrammable signature of cell identity that was revealed by specific efficiencies of conserved origin positions and not by the selection of cell type-specific subsets of origins.
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