Project A1: Checkpoint control in hematopoietic stem cells - contribution to genetic and epigenetic instability in leukemia
Prof. Dr. Hartmut Geiger
Institute of Molecular Medicine
University of Ulm
Life Sciences Building N27 and N24
Stem cells are frequently the underlying cancer-initiating cells, especially in leu-kemia. Leukemia is strongly associated with DNA mutations as well as changes in the epigenetic landscape of stem cells, implying a role for genetic and epigenetic instability in leukemia initiation and progression. Our novel preliminary data demonstrate that hematopoietic stem cells (HSC) do actively engage a mitotic check-point as well as a G2 checkpoint. Our novel hypothesis to test is that failure of activation of the mitotic check-point or other late cell cycle checkpoints (like the G2/M) will result in DNA mutations and/or alterations in the epigenetic architecture of stem cells upon subsequent division and by this means contribute to leukemia initi-ation and progression. Specific objectives are: (1) Define mechanisms of activation of the mitotic checkpoint in HSCs; (2) Determine consequences of a faulty checkpoint activation; and (3) Determine the role of Ube2g1 and cohesin in cell cycle checkpoint activation upon DNA damage.
For a current list of project-related publications, please go to this page