Journal
CELL CYCLE
Volume 11, Issue 4, Pages 658-667Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.11.4.19097
Keywords
DNA replication origins; DNA synthesis; G-quadruplex; nucleosome; CpG islands; transcription
Categories
Funding
- European Research Council [FP7/2007-2013, 233339]
- 'Agence Nationale de la Recherche' (ANR) [ANR-08-BLAN-0092-0]
- ARC
- 'Ligue Nationale Contre le Cancer' (LNCC)
- European Research Council (ERC) [233339] Funding Source: European Research Council (ERC)
- Agence Nationale de la Recherche (ANR) [ANR-08-BLAN-0092] Funding Source: Agence Nationale de la Recherche (ANR)
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We recently reported the identification and characterization of DNA replication origins (Oris) in metazoan cell lines. Here, we describe additional bioinformatic analyses showing that the previously identified GC-rich sequence elements form origin G-rich repeated elements (OGREs) that are present in 67% to 90% of the DNA replication origins from Drosophila to human cells, respectively. Our analyses also show that initiation of DNA synthesis takes place precisely at 160 bp (Drosophila) and 280 bp (mouse) from the OGRE. We also found that in most CpG islands, an OGRE is positioned in opposite orientation on each of the two DNA strands and detected two sites of initiation of DNA synthesis upstream or downstream of each OGRE. Conversely, Oris not associated with CpG islands have a single initiation site. OGRE density along chromosomes correlated with previously published replication timing data. Ori sequences centered on the OGRE are also predicted to have high intrinsic nucleosome occupancy. Finally, OGREs predict G-quadruplex structures at Oris that might be structural elements controlling the choice or activation of replication origins.
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