Kara A. Bernstein, PhD

Assistant Professor


Dr. Bernstein

Contact

412-864-7742
Fax: 412-623-1010

G.5C Hillman Cancer Center

5117 Centre Avenue

Pittsburgh, PA 15213-1862

Education

PhD in Genetics, Yale University

Research Summary

Repair of DNA damage is crucial to prevent accumulation of mutations that can cause human disease, such as cancer. Our lab studies how double-strand breaks in the DNA, one of the most lethal types of DNA lesions, are repaired. Many proteins are important for DNA repair including Sgs1, a protein that when mutated in human cells leads to many devastating diseases (i.e. Bloom, Werner, Rothmund-Thomson syndromes), which are all fundamentally characterized by cancer predisposition/premature aging. Sgs1 genetically interacts with a group of proteins collectively called the Shu complex. Although Sgs1 has been extensively analyzed, the molecular mechanism of how it functions to repair DNA damage and its relationship to the Shu complex has remained elusive, largely because its deletion leads to many pleiotropic phenotypes. Our lab uses cell biological, molecular, and genetic approaches to study the role of double-strand break repair proteins, such as Sgs1 and the Shu complex, in response to DNA damage. By understanding the mechanism of double-strand break repair and the role of DNA repair proteins in this process, we will uncover mechanisms of tumorigenesis and cancer progression. We will then use this knowledge to aid in diagnosis/prognosis of different types of cancers and to find novel therapeutic targets.

Research Lab Affiliation

Publications

Bernstein, K. A; Juanchich, A; Sunjevaric, I. and Rothstein, R. (2013) The Shu complex regulates Rad52 localization during rDNA repair. DNA Repair (Amst). [Epub ahead of print 06/25/2013] |  View Abstract

Godin, S; Wier, A; Kabbinavar, F; Bratton-Palmer, D. S; Ghodke, H; Van Houten, B; VanDemark, A. P. and Bernstein, K. A. (2013) The Shu complex interacts with Rad51 through the Rad51 paralogues Rad55-Rad57 to mediate error-free recombination. Nucleic Acids Res. 41: 4525-4534. |  View Abstract

Karpenshif, Y. and Bernstein, K. A. (2012) From yeast to mammals: recent advances in genetic control of homologous recombination. DNA Repair (Amst). 11: 781-788. |  View Abstract

Robert, T; Vanoli, F; Chiolo, I; Shubassi, G; Bernstein, K. A; Rothstein, R; Botrugno, O. A; Parazzoli, D; Oldani, A; Minucci, S; and Foiani, M. (2011) HDACs link the DNA damage response, processing of double-strand breaks and autophagy. Nature. 471: 74-79. |  View Abstract

Bernstein, K. A; Reid, R. J; Sunjevaric, I; Demuth, K; Burgess, R. C; and Rothstein, R. (2011) The Shu complex, which contains Rad51 paralogues, promotes DNA repair through inhibition of the Srs2 anti-recombinase. Mol Biol Cell. 22: 1599-1607. |  View Abstract

Bernstein, K. A; Gangloff, S; and Rothstein, R. (2010) The RecQ DNA helicases in DNA repair. Annu Rev Genet. 44: 393-417. |  View Abstract

Bernstein, K. A; and Rothstein, R. (2009) At loose ends: resecting a double-strand break. Cell. 137: 807-810. |  View Abstract