Mark Petronczki

Cell division and genomic stability

The physical separation of daughter cells during cytokinesis represents one of the most dramatic events of the eukaryotic cell cycle. After chromosomes have been segregated to opposite poles at anaphase, ingression of the cleavage furrow separates the cytoplasm of the nascent daughter cells.

In animal cells, cytokinesis requires the coordination of microtubule, actin, and membrane action. Tight temporal and spatial control of cytokinesis ensures that the segregated sets of chromosomes are equally partitioned into the daughter cells. Thereby, cytokinesis forms the basis for cell multiplication during proliferation and plays a key role in preventing aneuploidy, a hallmark of cancer cells. Recent experiments in murine cells have revealed that defects in cytokinesis lead to progressive aneuploidy and promote tumorigenesis.

Our newly established laboratory focuses on two major questions:

• What are the molecular mechanisms orchestrating cytokinesis in mammalian cells?
  Using a small-molecule inhibitor, we have recently discovered a key role for the mitotic kinase Plk1 in triggering the initiation of cytokinesis in human cells. Currently, we are investigating the molecular basis for how Plk1 controls cleavage furrow induction. Furthermore, we will use functional genomics and biochemistry to identify essential regulators of cytokinesis in human cells.



• What are the causes and consequences of cell division failure?
  We plan to use experimentally induced cytokinesis failure in mammalian cells as a tool to study the effects of tetraploidy on mitotic dynamics, genomic stability, and tumorigenesis. In addition, we plan to determine the spectrum of molecular lesions that are capable of causing cell division failure and tetraploidy.

We are looking for a motivated student, who is interested in cell division and aneuploidy, to join our team and take over one of the above projects.

References

Petronczki M, et al. Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle. Developmental Cell 2007; 12: 713-725.

Lénárt P, et al. The small-molecule inhibitor BI 2536 reveals novel insights into mitotic roles of polo-like kinase 1. Current Biology 2007; 17: 304-315.

Steegmaier M,et al. BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Current Biology 2007; 17: 316-322.

Gregan J, et al. Tandem affinity purification of functional TAP-tagged proteins from human cells. Nature Protocols 2007; 2: 1145-1151.

Petronczki M. Monopolar attachment of sister kinetochores at meiosis I requires casein kinase 1. Cell 2006; 126: 1049-1064.