EUKARYOTIC GENOME FUNCTIONS : ORDER FROM CLUTTER

Orateur : Arach GOLDAR (CEA Saclay)

The temporal, genomic and spatial organisation of genome functions (DNA replication and transcription) have puzzled cell biologists since early ages. The realisation that the genomic and the temporal organisation of transcription and replication are correlated and are influenced by chromatin compaction and its 3-dimensional folding deepened the fascination. Once it was discovered that these organisations are challenged in cancer and ageing, the understanding of cellular mechanisms that regulate these organisations becomes one of the major subject of research in cell biology. Many ideas about replication, transcription and chromatin organisation have been proposed, but most have been short on mechanistic details and some too detailed and specific. Therefore, a general and effective framework to describe the spatio-temporal organisation of genome function is missing. Here, using Saccharomyces cerevisiae as a model system and analytical approaches, I show how quantitative analysis of population based experimental data can unravel the emergent nature of replication and transcription process. Therefore invalidating the necessity of a hierarchal regulatory molecular mechanism. In the case of DNA replication, I show that by considering the stochastic nature of replication process one could link directly the dynamic and the distribution of replication origin activation to the chromatin compaction and its organisation in the nuclear volume.

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