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Papior, P. ; Arteaga-Salas, J.M.* ; Günther, T.* ; Grundhoff, A.* ; Schepers, A.

Open chromatin structures regulate the efficiencies of pre-RC formation and replication initiation in Epstein-Barr virus.

J. Cell Biol. 198, 509-528 (2012)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Whether or not metazoan replication initiates at random or specific but flexible sites is an unsolved question. The lack of sequence specificity in origin recognition complex (ORC) DNA binding complicates genome-scale chromatin immunoprecipitation (ChIP)-based studies. Epstein-Barr virus (EBV) persists as chromatinized minichromosomes that are replicated by the host replication machinery. We used EBV to investigate the link between zones of pre-replication complex (pre-RC) assembly, replication initiation, and micrococcal nuclease (MNase) sensitivity at different cell cycle stages in a genome-wide fashion. The dyad symmetry element (DS) of EBV's latent origin, a well-established and very efficient pre-RC assembly region, served as an internal control. We identified 64 pre-RC zones that correlate spatially with 57 short nascent strand (SNS) zones. MNase experiments revealed that pre-RC and SNS zones were linked to regions of increased MNase sensitivity, which is a marker of origin strength. Interestingly, although spatially correlated, pre-RC and SNS zones were characterized by different features. We propose that pre-RCs are formed at flexible but distinct sites, from which only a few are activated per single genome and cell cycle.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Origin Recognition Complex; Eukaryotic Dna-Replication; Nuclear Antigen-1; Saccharomyces-Cerevisiae; Dynamic Regulation; Latent Origin; Genome-Wide; Cell-Cycle; Sites; Transcription
ISSN (print) / ISBN 0021-9525
e-ISSN 1540-8140
Zeitschrift Journal of Cell Biology, The
Quellenangaben Band: 198, Heft: 4, Seiten: 509-528 Artikelnummer: , Supplement: ,
Verlag Rockefeller University Press
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)