Green BM, et al. (2006) Genome-wide mapping of DNA synthesis in Saccharomyces cerevisiae reveals that mechanisms preventing reinitiation of DNA replication are not redundant. Mol Biol Cell 17(5):2401-14
Abstract: Monitoring Editor: Orna Cohen-Fix To maintain genomic stability, reinitiation of eukaryotic DNA replication within a single cell cycle is blocked by multiple mechanisms that inactivate or remove replication proteins after G1 phase. Consistent with the prevailing notion that these mechanisms are redundant, we previously showed that simultaneous deregulation of three replication proteins, ORC, Cdc6 and Mcm2-7, was necessary to cause detectable bulk rereplication in G2/M phase in S. cerevisiae. In this study, we used microarray comparative genomic hybridization (CGH) to provide a more comprehensive and detailed analysis of rereplication. This genome-wide analysis suggests that reinitiation in G2/M phase primarily occurs at a subset of both active and latent origins, but is independent of chromosomal determinants that specify the use and timing of these origins in S phase. We demonstrate that rereplication can be induced within S phase, but differs in amount and location from rereplication in G2/M phase, illustrating the dynamic nature of DNA replication controls. Finally, we show that very limited rereplication can be detected by microarray CGH when only two replication proteins are deregulated, suggesting that the mechanisms blocking rereplication are not redundant. Therefore we propose that eukaryotic rereplication at levels below current detection limits may be more prevalent and a greater source of genomic instability than previously appreciated.
|Status: Published||Type: Journal Article||PubMed ID: 16481397|
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