Alexandra Sobeck, PhD

Associate Professor, and Biophysics Department of Biochemistry, Molecular Biology

Alexandra Sobeck

Contact Info

asobeck@umn.edu

Office Phone 612-624-1343

Mailing Address:
420 Washington Ave SE
Minneapolis, MN 55455

Associate Professor, and Biophysics Department of Biochemistry, Molecular Biology

Faculty, PhD Program in Biochemistry, Molecular Biology and Biophysics

Faculty, MS and PhD Programs in Pharmacology


Summary

Expertise

Cellular mechanisms, Genomic stability, DNA damage response, Chromosomal replication

Research

Research Summary/Interests

The stability of the cellular genome is constantly threatened by exogenous and endogenous mutagenic agents such as UV light or reactive oxygen species. 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.

Our lab is particularly interested in the evolutionarily new Fanconi anemia (FA) caretaker pathway.

According to the current FA pathway model, a large nuclear complex of at least ten FA proteins is required to activate two downstream target proteins, FANCD2 and FANCI, via monoubiquitination (see cartoon, Ub = Ubiquitin). 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 human cells as well as egg extracts from the African clawed frog, Xenopus laevis. Xenopus is 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 applies 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 FA proteins BRCA1 (FANCS) and BRCA2 (FANCD1), as well as non-FA DNA repair factors such as the BLM helicase or CtIP.