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Genome Biology 2011
Bright days for yeast researchAbstract: The annual British Yeast Group Meetings form a platform for high quality scientific interactions and have significant impact on the research directions followed. Here, we summarize talks and poster presentations on DNA replication dynamics and evolution, high-throughput screens and phenomics, chromatin biology and DNA damage presented at the meeting.Chromosomes must be correctly replicated before cell division, as aberrant replication can cause genome instability. Therefore, origins of replication must be tightly regulated and appropriately distributed in the genome. Michelle Hawkins (University of Nottingham, UK) discussed the genome-wide measurement of DNA copy numbers from synchronized budding yeast cell populations as they progress through S phase. Using next-generation sequencing, replication profiles were generated. The data obtained were then combined with a mathematical model of DNA replication, which enabled predictions of individual origin properties that largely agree with independent experimental data. The model predicts cell-to-cell variations, the distribution of distances between active origins and the number of replication forks. These studies resulted in a data-rich platform that will be used to understand the mechanisms involved in faithful and precise DNA replication.Origins of replication fall into three categories - early, late and dormant - because for unknown reasons they do not initiate simultaneously at the beginning of the S phase. Two kinase activities are required for replication initiation throughout S phase: cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK). Philip Zegerman (Gurdon Institute, University of Cambridge, UK) showed that substrates of CDK (Sld2, Sld3 and their binding partner Dpb11) and the DDK subunit Dbf4 are limiting factors for replication initiation in budding yeast. Overexpression of these factors led to early initiation of late origins. When such overexpression was combined with deletion of the histone dea
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