Person:

Senaratne, Niroshi Niroshini

The organization of interphase nuclei has numerous consequences for gene expression and genome stability in eukaryotes. Here, we present studies of chromosome organization in Drosophila melanogaster over the course of the cell cycle. We report surprising observations suggesting that cohesin, a protein complex essential in mitosis for holding together the products of DNA replication known as sister chromatids, may not be required to keep sister chromatids in close proximity during interphase. These observations raise questions regarding the nature of cohesin-independent connections between chromatids, why the cell might have such connections in addition to those mediated by cohesin proteins, and how cohesin-independent mechanisms might contribute to other inter-chromosomal associations and nuclear organization throughout the cell cycle. A well-known feature of nuclear organization in Drosophila is the somatic pairing of maternal and paternal homologous chromosomes; we find that certain factors contributing to the pairing of homologs, specifically, condensin II and its regulators, also contribute to the organization of sister chromatids, findings which have interesting implications for the nature of pairing. Finally, we examine another type of inter-chromosomal interaction occurring in Drosophila nuclei, which is the nonhomologous clustering of centromeres, and identify candidate genes that regulate this organization. Overall, this work expands current knowledge on both homologous and heterologous inter-chromosomal interactions, and highlights the relationship between chromosome organization in interphase and in mitosis.