Our lab is interested in the mechanisms that regulate chromosome segregation and thereby contribute to maintain genome stability. In particular, we focus on the mechanisms of sister chromatid cohesion and centromere specification.
Cohesin, a multiprotein complex conserved from yeast to human, is a prominent mediator of sister chromatid cohesion. We are using Xenopus laevis egg extracts and mammalian cells to study the regulation of cohesin. Of special interest is the relationship between cohesin and the replication machinery, as well as the dissolution of cohesion in mitosis. We are also developing mouse models of cohesion factors to explore their potential role in development and tumorigenesis.
In the metaphase chromosomes of most eukaryotes, the centromere is cytologically visible as a primary constriction embedded in heterochromatin. This chromosomal locus is epigenetically determined by the presence of CENP-A, a histone H3 variant. A central question is how CENP-A is incorporated specifically into centromeric chromatin and when this happens. We are taking several approaches to address this question: proteomic identification of CENP-A associated factors, development of a CENP-A incorporation assay in Xenopus egg extracts and screening of RNAi libraries (siRNA or shRNA) in human cells.
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Targeting of Bub1 to kinetochores in human mitotic cells is independent of Aurora B. Immunofluorescent staining of control and Aurora B knocked down HeLa cells with antibodies against Aurora B (red) and Bub1 (red) and counterstained with DAPI (blue).