The research program of the Kellum lab focuses on how the DNA of eukaryotic cells is organized into functional chromosomes. A primary area of interest is on highly compact regions of the chromosomes with specialized functions in chromosome maintenance and gene regulation. We have used a combination of biochemical, genetic, cytological, and molecular tools offered by the experimentally tractable model organism of Drosophila to purify and characterize a complex of proteins associated with a highly conserved component of these compact regions, also known as heterochromatin. This heterochromatin protein (HP1) complex contains subunits of the Origin Recognition Complex, known to bind and recruit DNA replication factors to specific sequences in the initiation of DNA replication. The association of this heterochromatin protein with DNA replication proteins suggests a mechanism for linking the process of heterochromatin assembly to that of DNA replication. This complex contains a second previously uncharacterized DNA-binding activity that we have designated as HP1/ORC-Associated Protein (HOAP). We have found this protein to function in the assembly of a specific heterochromatic structure at chromosome ends that prevents them from undergoing end-to-end fusions. The lab is now taking advantage of modern genomics tools to identify binding sequences for ORC and HOAP in heterochromatin that could function in either the establishment or maintenance of heterochromatin assembly during DNA replication.