Sobeck lab: Difference between revisions
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Revision as of 20:54, 11 March 2009
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Contact Info
- Alexandra Sobeck
- Assistant professor, University of Minnesota, Minneapolis
- 420 Washington Ave SE, MCB 6-112
- Minneapolis, MN 55455
- asobeck@umn.edu
We just started our new lab in Jan 2009, and will use OWW to create our own fun lab homepage for introducing ourselves + our research, sharing protocols, scheduling lab meetings, etc...
People
Karl Herman
Brittany Feia
Jill Kleidon
Alex Sobeck
more info coming soon ...
Education
Research interests
Research Description The stability of the cellular genome is constantly threatened by a variety of exogenous and endogenous mutagenic agents such as UV light, reactive oxygen species, etc. Cells protect their genome against carcinogenic alterations by using a complex network of “caretaker” proteins that function to maintain the integrity of the cellular chromosomes. Inherited defects in these caretaker genes are the cause of genomic instability syndromes in humans, such as Fanconi Anemia or Bloom syndrome, characterized by a highly elevated risk to develop certain types of cancer. We study these diseases to understand and discover novel mechanisms important to control and suppress cancer susceptibility.
We ares particularly interested in the evolutionarily new Fanconi anemia (FA) caretaker pathway. According to the current FA pathway model (see cartoon), a large nuclear complex of at least 10 FA proteins is required to activate two downstream target proteins, FANCD2 and FANCI. This activation occurs in response to DNA damage but also during every S-phase of the cell cycle, when cells replicate their chromosomes. Thus, the FA pathway is suspected to have important functions to prevent DNA damage that occurs naturally during every round of chromosomal replication.
To identify the roles of FA proteins in the DNA damage response, we use egg extracts from the African clawed frog Xenopus laevis – an extremely powerful cell free system that uniquely mirrors cellular replication of DNA complete with the assembly of chromatin into a functional nucleus.
The lab uses a combination of biochemistry, genetics, and imaging techniques to elucidate molecular mechanisms that underlie the FA caretaker functions, and to understand how FA proteins are networked with other caretaker proteins including the breast cancer-associated proteins (e.g. BRCA1 and BRCA2) and the Bloom syndrome-associated proteins (e.g. BLM and BLAP75).
Published Articles
- Landais I*, Sobeck A*, Stone S*, LaChapelle A, Hoatlin ME (2008): A novel cell-free screen identifies a potent inhibitor of the Fanconi anemia pathway. Int. J. Cancer, in press. (Cover)
- Xu D*, Guo R*, Sobeck A, Bachrati CZ, Yang J, Enomoto T, Brown GW, Hoatlin ME, Hickson ID, Wang W (2008): RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability. Genes Dev 22: 2843-55.
- Sobeck A, Stone S, Hoatlin ME (2007): DNA Structure-Induced Recruitment and Activation of the Fanconi Anemia Pathway Protein, FANCD2. Mol Cell Biol 27: 4283-92.
- Stone S, Sobeck A, Margriet van Kogelenberg, Bendert de Graaf, Hans Joenje, Jan Christian, Hoatlin ME (2007): Identification, Developmental Expression, and Regulation of the Xenopus Ortholog of Human FANCG/XRCC9. Genes Cells, 12: 841-51.
- Sobeck A*, Stone S*, Costanzo V, de Graaf B, Reuter T, de Winter J, Wallisch M, Akkari Y, Olson S, Wang W, Joenje H, Christian JL, Lupardus PJ, Cimprich KA, Gautier J, Hoatlin ME (2006): Fanconi anemia proteins are required to prevent accumulation of replication-associated DNA double-strand breaks. Mol Cell Biol 26: 425-37. (Cover)
- Yin J*, Sobeck A*, Xu C*, Meetei AR, Hoatlin M, Li L, Wang W (2005): BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity. EMBO J. 24: 1465-76.
- Leveille F, Blom E, Medhurst AL, Bier P, Laghmani el H, Johnson M, Rooimans MA, Sobeck A, Waisfisz Q, Arwert F, Patel KJ, Hoatlin ME, Joenje H, de Winter JP (2004): The Fanconi anemia gene product FANCF is a flexible adaptor protein. J Biol Chem. 279: 39421-30.
- U. Oppitz, U. Bernthaler, D. Schindler, A. Sobeck, H. Hoehn, M. Platzer, A. Rosenthal, and M Flentje (1999): Sequence Analysis of the ATM Gene in 20 Patients with RTOG grade 3 or 4 Acute and/or Late Tissue Radiation Side Effects. Int. J. Radiation Oncology Biol. Phys. 44, 981-988.
- K.J. Erb, J.W. Holloway, A. Sobeck, H. Moll, G. Le Gros (1998): Infection of mice with Mycobacterium bovis-Bacillus Calmette-Guerin (BCG) suppresses allergen-induced airway eosinophilia. J Exp Med 187:561-9.
Useful links
