University of Pittsburgh Cancer Institute (UPCI)

Genome Stability

ERCC1Genomic instability is a major cause of tumor formation. During cell division, genomic instability is minimized by high-fidelity DNA replication in S-phase, precise chromosome segregation in mitosis, error-free repair of sporadic DNA damage, and coordinated cell cycle progression. Alterations in these processes can cause cellular senescence and premature aging or tumor formation.

Selected Publications

  • One difficulty in treating glioblastoma is the development of resistance to the chemotherapeutic agent, temozolomide. Base excision repair (BER) is an important pathway which removes alkylated bases that result from temozolomide. Incomplete BER causes long-lived strand breaks which stimulates poly-ADP-ribose polymerase and causes a subsequent depletion in NAD. Combination therapy is a promising approach to overcome resistance to chemotherapeutic drugs. Glioblastoma cells that are highly resistant to temozolomide could be killed by combining an inhibitor of BER with an inhibitor of NAD synthesis (Goellner EM, et. al., Cancer Res. 71:2308-17, 2011).
  • In yeast, the Shu complex, which contains RAD51 paralogues, is involved in the decision between homologous recombination and error-prone repair. The Shu complex shifts the balance of repair toward Rad51 filament stabilization by inhibiting the disassembly reaction of Srs2 (Bernstein KA, et. al., Mol Biol Cell 22:1599-607, 2011).

Members

Bahar, Ivet, PhD
Computational and Systems Biology
Sobol, Robert, PhD
Pharmacology and Chemical Biology
Bakkenist, Christopher, PhD
Radiation Oncology
Van Houten, Ben, PhD
Pharmacology and Chemical Biology
Bernstein, Kara, PhD
Microbiology and Molecular Genetics
Wan, Yong, PhD
Cell Biology and Physiology
Lan, Li, MD, PhD
Microbiology and Molecular Genetics
Watkins, Simon, PhD
Cell Biology and Physiology
Opresko, Patricia, PhD
Environmental and Occupational Health