Robert Wood Johnson Medical School
Department of Biochemistry & Molecular Biology
RWJMS Research Building, Room 284
683 Hoes Lane West
Piscataway, NJ 08854
Sister chromatid cohesion; gene expression; chromatin and epigenetics
DNA replication generates pairs of sister chromatids that are held together until anaphase by a protein complex named cohesin. The phenomenon, termed sister chromatid cohesion, is critical for the proper loading of chromatids onto mitotic and meiotic spindles. Defects in the cohesion pathway give way to chromosome instability that accompanies cancers and certain developmental diseases. In Roberts-SC phocomelia syndrome specifically, cohesion is strikingly absent from chromosomal domains bearing heterochromatin, a form of chromatin that was initially thought to package the “junk” DNA of eukaryotic genomes. Heterochromatin is now known to play critical roles in the nucleus, ranging from maintaining proper chromosome segregation to regulating gene expression at the level of transcription. Heterochromatin domains are distinguished at the molecular level by specialized histone modifications and non-histone binding proteins. The structure is passed from one generation to the next in a heritable manner that has become a paradigm of epigenetic control.
My lab has held a long-standing interest in the ways that heterochromatin is assembled, maintained and inherited. Our recent work includes focus on the specialized roles of heterochromatin in sister chromatid cohesion. We use the budding yeast Saccharomyces cerevisiae as a model eukaryotic system where we have developed molecular biological tools to ask questions at the mechanistic level.