We are interested in understanding the mechanisms by which the molecular architecture of the chromosome regulates fundamental biological processes such as replication and transcription. Specifically, how are replication, transcription and chromatin modification coordinated on a genomic scale to maintain genomic stability? We are addressing this question by using genomic, computational and biochemical approaches in multiple model systems including Drosophila melanogaster, Saccharomyces cerevisiae and mammalian cell culture.