The regulation of DNA replication in animal cells is of utmost importance for understanding cell growth and transformation. In order to study this process, we have developed a novel assay which measures replication directions and allows one to define chromosomal replication units by identifying both origins and termination sites. This approach has proved useful for deciphering the cis acting elements which regulate replication in the human beta globin gene locus, and will serve as a basis for understanding the structure and function of tissue specific chromosomal domains. DNA replication timing during the cell cycle is developmentally regulated and probably plays a role in the control of gene expression. A new approach for measuring replication timing of individual genes which involves in situ hybridization to interphase nuclei will be used to study this process on dividing cells both in vitro and in vivo. These findings allow one, for the first time, to define chromosomal bands at the molecular level and to decipher what role they play in the organization of the genome. Regional replication timing also appears to play a role in the control of parental imprinting both in mice and in man. Understanding this phenomenon may help elucidate the molecular mechanisms of controlling gene expression in genetic diseases, such as the Prader-Willi and Angelman syndromes, in the retinoblastoma and Wilm's tumor syndromes and in the chromosomal translocations characteristic of leukemia.
