Kara Anne Bernstein, Ph.D.

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Professor of Biochemistry and Biophysics
Department: Biochemistry and Biophysics

Contact information
Philadelphia, PA 19104-6059
B.A. (Biology)
Bryn Mawr College, 2000.
M.Phil. (Genetics)
Yale University, 2004.
Ph.D. (Genetics)
Yale University, 2006.
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Description of Research Expertise

Research Interests:

My research focuses on proteins that contribute to cancer development and studies how accurate repair of DNA double-strand breaks is regulated using the budding yeast and mammalian systems.


DNA repair and recombination, breast and ovarian cancer, double-strand break repair

Research Details:

Breast and ovarian cancer can be caused by a combination of our environmental exposures as well as our genetic make-up. Family history of breast and ovarian cancer can be used to predict whether or not an individual needs additional screening or testing. Our research focuses on proteins that contribute to breast and ovarian cancer development and studies how accurate repair of DNA double-strand breaks is regulated using the budding yeast and mammalian systems. We have been focusing on the DNA repair genes, the RAD51 paralogs, which when mutated lead to increased breast and ovarian cancer risk using genetic, biochemical, and cell biological approaches. By understanding RAD51 paralog molecular function, the our lab aims to determine individuals who are at risk for cancer development and how cancer risk is compounded upon exposure to environmental toxicants that damage DNA.

Rotation Projects:

My lab studies mechanisms of cancer development and how misregulation of DNA repair genes contributes to genetic instability and tumorigenesis. Part of my lab uses mammalian cells to study the RAD51 paralogs, genes that are mutated in hereditary breast and ovarian cancer, to determine their molecular function and to analyze patient derived mutations for DNA repair defects using genetics, molecular biology, and cell biology techniques. The other part of my laboratory uses the budding yeast system to dissect RAD51 paralog molecular function using genetic, biochemical, and molecular biology techniques.

Project 1: To analyze RAD51 paralog cancer-identified mutations for altered protein interactions and DNA repair defects using yeast-2-hybrid system and mammalian cell recombination reporter assays. This project will enable reclassification of variants of unknown function significance as pathogenic or benign.

Project 2: To analyze RAD51 paralog function during DNA replication using the budding yeast system to uncouple a new functional interaction between the RAD51 paralogs and the MCM complex. This project will analyze protein interactions and also use genetic and molecular biology techniques to uncover separation-of-function alleles.

Lab Personnel:

Adeola Fagunloye (PhD student, BMB)
Azrin Jamalruddin (PhD sudent, BMB)
Kristie Darrah (Post-Doctoral Fellow)
Phoebe Parker (Technician)

Selected Publications

Rawal, Y., Jia, L., Meir, A., Zhou, S., Kaur, H., Ruben, E.A., Kwon, Y., Bernstein, K.A., Jasin, M., Taylor, A.B., Burma, S., Hromas, R., Mazin, A.V., Zhao, W., Zhou, D., Wasmuth, E.V., Greene, E.C., Sung, P., Olsen, S.K. : Structural insights into BCDX2 complex function in homologous recombination. Nature 619(7970): 640-649, 2023.

Rein, H.L. and Bernstein, K.A.: Finding significance: New perspectives in variant classification of the RAD51 regulators, BRCA2 and beyond. DNA Repair 130: 103563, 2023.

Toland, S., Robinson-McCarthy L.R., Lee, N., Schaich, M.A., Hengel, S.A., Li, X., Bernstein, K.A., Van Houten, B., Chang, Y., Moore, P.S. : Unlicensed origin DNA melting by MCV and SV40 polyomavirus LT proteins does not require an active helicase enzyme. Proceedings of the National Academy of Sciences 120(30): e2308010120, 2023.

Prakash, R.*, Rawal, Y., Sullivan, M.R., Grundy, M.K., Bret, H., Mihalevic, M.J., Rein, H.L., Baird, J.M., Darrah, K., Zhang, F., Wang, R., Traina, T.A., Radke, M.R., Kaufmann, S.H., Swisher, E.M., Guérois, R., Modesti, M., Sung, P., Jasin, M.*, Bernstein, K.A.* *Co-corresponding: Homologous recombination deficient mutation cluster in tumor suppressor RAD51C identified by comprehensive analysis of cancer variants Proceedings of the National Academy of Science 119(38): e2202727119, 2022.

Bai, S., Taylor, S.E., Jamalruddin, M.A., McGonigal, S., Grimley, E., Yang, D., Bernstein, K.A., and Buckanovich, R.J. : Targeting therapeutic resistance and multinucleate giant cells in CCNE1-amplified HR-proficient ovarian cancer. Molecular Cancer Therapeutics 2022.

Luong, T.T., Li, Z., Priedigkeit, N., Parker, P.S., Böhm, S., Rapchak, K., Lee, A.V., Bernstein, K.A.: Hrq1/RECQL4 regulation is critical for preventing aberrant recombination during DNA intrastrand crosslink repair and is upregulated in breast cancer. PLoS Genetics 18(9): e1010122, 2022.

Bonilla, B., Brown, A.J., Hengel, S.R., Rapchak, K.S., Mitchell, D., Pressimone, C.A., Fagunloye, A.A., Luong, T.T., Russell, R.A., Vyas, R.K., Mertz, T.M., Zaher, H.S., Mosammaparast, N., Malc, E.P., Mieczkowski, P.A., Roberts, S.A.*, Bernstein, K.A.*: The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions. eLife 10: e68080, 2021.

Sullivan MR, Prakash R, Rawal Y, Wang W, Sung P, Radke MR, Kaufmann SH, Swisher EM, Bernstein KA, Jasin M.: Long-term survival of an ovarian cancer patient harboring a RAD51C missense mutation. Cold Spring Harbor Molecular Case Studies 7: a006083, 2021.

Prakash R, Sandoval T, Morati F, Zagelbaum JA, Lim PX, White T, Taylor B, Wang R, Desclos ECB, Sullivan MR, Rein HL, Bernstein KA, Krawczyk PM, Gautier J, Modesti M, Vanoli F, Jasin M.: Distinct pathways of homologous recombination controlled by the SWS1-SWSAP1-SPIDR complex. Nature Communications 12: 4255, 2021.

Rein HL, Bernstein KA, Baldock RA.: RAD51 paralog function in replicative DNA damage and tolerance. Current Opinion in Genetics & Development 71: 86-91, 2021.

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Last updated: 02/26/2024
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