"ORCanization" on heterochromatin: linking DNA replication initiation to chromatin organization

Abstract

Specialized complexes in eukaryotic cells recognize defined epigenetic histone marks to mediate chromatin organization. DNA replication, cell cycle progression and chromatin organization are intimately linked to one another. In addition to having roles in DNA replication initiation, the human Origin Recognition Complex (ORC) binds along with ORC-associated proteins ORCA/ LRWD1 to prominent transcriptional repressive lysine methylation marks and localizes to HP1-containing heterochromatic structures. In humans, Drosophila and Xenopus, ORC associates with HP1, and this interaction is crucial for heterochromatin organization. Further, several subunits of human ORC are required for centromere and telomere function and participate in chromosome segregation. The conserved function of ORC in replication initiation as well as in organization and maintenance of chromosome structure suggests that these cellular events are well coordinated.