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- Title
Unraveling cell type-specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs.
- Authors
Besnard, Emilie; Babled, Amélie; Lapasset, Laure; Milhavet, Ollivier; Parrinello, Hugues; Dantec, Christelle; Marin, Jean-Michel; Lemaitre, Jean-Marc
- Abstract
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.
- Subjects
DNA replication; QUADRUPLEX nucleic acids; INDUCED pluripotent stem cells; CELL cycle; POLYMERASE chain reaction
- Publication
Nature Structural & Molecular Biology, 2012, Vol 19, Issue 8, p837
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.2339