Terry L. Orr-Weaver

By investigating the regulation of cell division during metazoan development we have discovered proteins crucial for the proper regulation of DNA replication and chromosome segregation that are conserved to humans. We exploited genetic approaches in Drosophila melanogaster and variant cell cycles that highlight and permit analysis of DNA replication and chromosome segregation to recover mutants that uncovered control proteins. These studies identified the MEI-S332 protein, founding member of the Shugoshin family, by its essential role at the centromere to promote cohesion and accurate chromosome segregation. We isolated a protein kinase complex that promotes mitosis by regulating the translation of Cyclin B. We defined the Dup/Cdt1 protein family, a conserved family of proteins that is the crucial factor in triggering the initiation of DNA replication from yeast to human cells. Our work identified the first binding site for the Origin Recognition Complex in metazoans and revealed a direct role for the Retinoblastoma tumor suppressor protein in DNA replication. This work unraveled mechanisms by which differential DNA replication is employed as a developmental strategy. We demonstrated the role of a histone code in chromosome dynamics in meiosis.