Alexandra Sobeck

I will be starting my own laboratory at the University of Minnesota in Minneapolis in January 2009.

Alexandra Sobeck, Ph.D. Postdoctoral Fellow

Alex received her Ph.D. in Human Genetics at the Julius-Maximilians-University, Wuerzburg, Germany in 2002 after earning her M.S. in biochemistry from the Julius-Maximilians-University in 1998. She arrived at OHSU in June 2002 and is currently funded as a postdoctoral fellow by the American Heart Association. Alex enjoys caffeine in huge quantities, tennis, soccer, mosaics and working late hours.

Research Interest

We and others have shown that the upstream FA core complex is required for replication-dependent activation (monoubiquitination) of the downstream FANCD2 protein in response to DNA damaging agents that stall the replication fork. Our lab could also demonstrate that depletion of FA proteins from Xenopus laevis egg extracts results in accumulation of chromosomal breaks during replicative DNA synthesis.

To further elucidate FA pathway function(s) in the replication-coupled DNA damage response I am interested in determining which DNA repair intermediates lead to specific recruitment and activation of the FA proteins. I am currently developing an activation assay in Xenopus egg extracts to test DNA minisubstrates for their ability to recruit and activate the FA core complex and/or FANCD2. Within the same experimental setting, I am using single-protein depletion strategies to investigate how the FA pathway is intertwined with other central DNA repair pathways in the DNA structure-specific damage response.

Published Articles

• 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.

• 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.

Abstracts + Talks

• A. Sobeck, S. Stone, A.M. LaChapelle, I. Landais and M.E. Hoatlin (2007): Differential ACtivation of Core Complex Member FANCM and Downstream Target FANCD2 during the DNA Damage Response (oral presentation). Fanconi Anemia Research Fund, scientific symposium (Chicago, IL).
• A. Sobeck, S. Stone, A.M. LaChapelle, K.A. Cimprich, J. Gautier and M.E. Hoatlin (2006): Regulated Recruitment of Fanconi Anemia Proteins to DNA Replication and Repair Intermediates (abstract). Fanconi Anemia Research Fund, scientific symposium (Bethesda, MD).
• A. Sobeck, S. Stone, V. Costanzo, W. Wang, H. Joenje, J. Gautier and M.E. Hoatlin (2005): Partial Overlap of FANCD2 and Mre11 Pathways in Response to DNA Repair Intermediates (oral presentation). Fanconi Anemia Research Fund, scientific symposium (Geneva, Switzerland).
• A. Sobeck, S. Stone, B. de Graaf, V. Costanzo, J. de Winter, W. Wang, H. Joenje, J. Gautier and M.E. Hoatlin (2004): FA Proteins and Caretaker Networks: The Chain of Command (oral presentation). Fanconi Anemia Research Fund, scientific symposium (Cambridge, MA).
• A. Sobeck, V. Costanzo, S. Stone, B. de Graaf, T. Reuter, J. de Winter, M. Wallisch, W. Wang, H. Joenje, J. Gautier, and M.E. Hoatlin (2004). FA Proteins and Caretaker Networks (oral presentation). Mechanisms of Genomic Integrity, Workshop (Galway, Ireland).
• A. Sobeck, V. Costanzo, S. Stone, B.R. de Graaf, T. Reuter, J. de Winter, M. Wallisch, H. Joenje, J. Gautier, and M.E. Hoatlin (2003): Xenopus FANCD2 Binds to Chromatin in a Replication and DNA Damage-Dependent Manner (oral presentation). Fanconi Anemia Research Fund, scientific symposium (Houston, TX).
• S. Stone, B.R. de Graaf, A. Oostra, M. Wallisch, A. Sobeck, P. Bier, J. de Winter, H. Joenje and M.E. Hoatlin. (2003): The Fanconi Anemia Pathway is Functionally Conserved in Xenopus (abstract). Fanconi Anemia Research Fund, scientific symposium (Houston, TX).
• S. Stone, A. Sobeck, T. Reuter, I. Bijsmans, Y. Akkari, S. Olson, Q. Waisfisz, J. de Winter, H. Joenje, J. Christian and M. Hoatlin (2003): A Fanconi Anemia-Like Phenotype Induced in Xenopus laevis (abstract): Gordon Research Conference on Cancer genetics and Epigenetics.
• A. Sobeck, D. Schindler, R. Bendix, T. Dörk (2001) Three new exons of the ATM gene activated by aberrant splicing due to intronic mutations. (abstract) Eur J Hum Genet 9: P-0741.
• H. Siebert, A. Sobeck, D. Schindler (2000) Mutation analysis on 19 ataxia telangiectasia patients between 19 and 37 years of age. (abstract) Eur J Hum Genet 8: P-596.
• A. Sobeck, M. Wagner, S. Herterich, G. Emmert, U. Oppitz, M. Flentje, H. Hoehn and D. Schindler (1998) Mutation Analysis in the Ataxia Telangiectasia Gene, ATM. (abstract) Med Genet 1: P7-116.

Other Stuff

Invited talks

• A Leap towards Understanding Genomic Integrity: Xenopus laevis as a New Model to Decipher the Fanconi Anemia/BRCA Caretaker Pathways (2007). Department of Genetics and Complex Diseases, Harvard School of Public Health.
• Unravelling the Function of the Fanconi Anemia Pathway Proteins in DNA Replication (2005). Cancer Research UK, Clare Hall Laboratories (guest of Dr. V. Costanzo)

Invited Papers

• A. Sobeck and M. Wagner (2002): Interactions between Fanconi and RAD51 Proteins in the Yeast 2-Hybrid System (german). Medizinische Genetik Edition 2: Fanconi Anaemie.

• D. Schindler, A. Sobeck (1999): Diagnostics of Ataxia telangiectasia by flow cytometry and cell cycle analysis (german). Medizinische Genetik Edition Band 1: Ataxia teleangiectatica.

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