Jeff Bachant
Assistant Professor of Cell Biology
|
Ph.D, University of Colorado, Cellular Biology, 1993
|
Mitosis is a precisely regulated event during which equivalent sets of chromosomes are partitioned between mother and daughter cells. Research in this lab is focused on the mechanisms that ensure accurate mitotic chromosome transmission and that make mitotic entry responsive to stressful contingencies. One area of study is to elucidate how replicated pairs of chromosomes are physically held together, or cohesed, until the onset of chromosome segregation. Cohesive linkages between sister chromatids are thought to enable chromatid pairs to achieve bipolar attachment to the mitotic spindle. Centromeric regions of chromosomes appear to be specialized sites of sister chromatid association, but the processes that control this aspect of centromere function are not well understood. We are utilizing the budding yeast S. cerevisiae to investigate how cohesion is regulated at centromeres through the analysis of mutants that disrupt chromatid associations at centric regions. Other projects are focused on understanding how chromosome segregation is delayed following activation of the checkpoint pathways that allow cells to respond to DNA damage or blocks to DNA replication. In S. cerevisiae, DNA damage checkpoints prevent chromosome segregation by blocking cells in a pre-anaphase state. Analysis of this response may illuminate regulatory pressure points controlling mitotic spindle function and the timing of chromosome segregation.
Representative Publications:
Bachant J, A Alcasabas, Y Blat, N Kleckner and SJ Elledge. A role for the SUMO-1 isopeptidase Smt4 and DNA Topoismerase II in control of centromeric cohesion. Molecular Cell, in press.
Li Y, J Bachant, AA Alcasabas, J Qin and SJ Elledge (2002). The mitotic spindle is required for loading the DASH complex onto the kinetochore. Genes & Dev. 16: 183-197.
Alcasabas AA, AJ Osborn, J Bachant, F Hu, PJH Werler, K Bousset, K Furuya, JFX Diffley, A Carr and SJ Elledge (2001). Mediator of the DNA Replication Checkpoint, MRC1, Transduces DNA Replication Stress Signals to Activate Rad53. Nature Cell Biology 3: 958-965.
Sanchez Y, J Bachant, H Wang, M Tetzlaff and SJ Elledge (1999). S. cerevisiae Chk1 and Rad53 kinases inhibit anaphase through distinct mechanisms following DNA damage. Science 286:1166-1171.
Jones SH, JB Bachant, AR Castillo, TH Giddings and M Winey (1999). Yeast Dam1p is required to maintain spindle integrity during mitosis and interacts with the Mps1 kinase. Mol. Biol. Cell 10:2377-2391.
Desany BA, AA Alcasabas, JB Bachant and SJ Elledge (1998). Recovery from DNA replicational stress is the essential function of the S phase checkpoint pathway. Genes & Dev. 12:2956-2970.