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Kara Anne Bernstein, Ph.D.
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George W. Raiziss Professor in Biochemistry and Biophysics II
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Department: Biochemistry and Biophysics
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Graduate Group Affiliations
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Contact information
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N/A
Philadelphia, PA 19104-6059
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Philadelphia, PA 19104-6059
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Office: 215-746-6264
3e Lab: 215-746-6265
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3e Lab: 215-746-6265
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Publications
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Education:
21 9 B.A. 14 (Biology) c
2a Bryn Mawr College, 2000.
21 c M.Phil. 15 (Genetics) c
28 Yale University, 2004.
21 a Ph.D. 15 (Genetics) c
28 Yale University, 2006.
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Permanent link21 9 B.A. 14 (Biology) c
2a Bryn Mawr College, 2000.
21 c M.Phil. 15 (Genetics) c
28 Yale University, 2004.
21 a Ph.D. 15 (Genetics) c
28 Yale University, 2006.
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c6 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.
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12 Keywords:
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5b DNA repair and recombination, breast and ovarian cancer, double-strand break repair
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1a Research Details:
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37b 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.
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1a Rotation Projects:
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269 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.
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13e 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.
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154 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.
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16 Lab Personnel:
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2c Azrin Jamalruddin (PhD student, BMB)
27 Tanis Dorwart (PhD student, CB)
28 Noah Goff (Post-Doctoral Fellow)
2c Anna Palovcak (Post-Doctoral Fellow)
24 Gayatri Ganesan (Technician)
24 Zoe Moosbrugger (Technician)
1e Jehan Mody (Technician)
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Description of Research Expertise
26 Research Interests:8
c6 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.
8
12 Keywords:
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5b DNA repair and recombination, breast and ovarian cancer, double-strand break repair
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1a Research Details:
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37b 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.
8
1a Rotation Projects:
8
269 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.
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13e 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.
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154 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.
8
16 Lab Personnel:
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2c Azrin Jamalruddin (PhD student, BMB)
27 Tanis Dorwart (PhD student, CB)
28 Noah Goff (Post-Doctoral Fellow)
2c Anna Palovcak (Post-Doctoral Fellow)
24 Gayatri Ganesan (Technician)
24 Zoe Moosbrugger (Technician)
1e Jehan Mody (Technician)
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1fd Rein, H.L., Rawal, Y., Palovcak-Lightbourn, A.L., Ganesan, G., Parker, P., Russell, R., Darrah, K., Afsar, M., Sullivan, M.R., Hengel, S.R., Radke, M.R., Opresko, P.L., Yanowitz, J.L., Greene, E.C., Lee, J.M., Domchek, S.M., Swisher, E.M., Olsen, S.K., Sung, P., Bernstein, K.A. : Comprehensive RAD51C ovarian cancer variant analysis uncouples homologous recombination and replicative functions. Nature Communications 16(1): 6539, 2025.
17b Hengel, S.R., Oppenheimer, K., Smith, C.M., Schaich, M.A., Rein, H.L., Martino, J., Darrah, K.E., Witham, M., Ezekwenna, O.C., Burton, K., Van Houten, B., Spies, M., Bernstein, K.A.: The human Shu complex promotes RAD51 activity by modulating RPA dynamics on ssDNA. Nature Communications 15(1): 7197, 2024.
f8 Rein, H.L., Bernstein, K.A.: Variants in the first methionine of RAD51C are homologous recombination proficient due to an alternative start site. DNA Repair 135: 103644, 2024.
196 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.
f3 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.
193 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.
155 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.
236 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.
16b 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.
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Selected Publications
156 Fagunloye, A.A., DeMagis, A., Little, J.H., Contreras, I., Dorwart, T.J., Bonilla, B., Gupa, K., Clark, N., Zacheji, T., Paeschke, K.*, Bernstein, K.A.* : The Shu complex interacts with the replicative helicase to bypass DNA damage. EMBO Journal 44(5): 1512-1539, 2025.1fd Rein, H.L., Rawal, Y., Palovcak-Lightbourn, A.L., Ganesan, G., Parker, P., Russell, R., Darrah, K., Afsar, M., Sullivan, M.R., Hengel, S.R., Radke, M.R., Opresko, P.L., Yanowitz, J.L., Greene, E.C., Lee, J.M., Domchek, S.M., Swisher, E.M., Olsen, S.K., Sung, P., Bernstein, K.A. : Comprehensive RAD51C ovarian cancer variant analysis uncouples homologous recombination and replicative functions. Nature Communications 16(1): 6539, 2025.
17b Hengel, S.R., Oppenheimer, K., Smith, C.M., Schaich, M.A., Rein, H.L., Martino, J., Darrah, K.E., Witham, M., Ezekwenna, O.C., Burton, K., Van Houten, B., Spies, M., Bernstein, K.A.: The human Shu complex promotes RAD51 activity by modulating RPA dynamics on ssDNA. Nature Communications 15(1): 7197, 2024.
f8 Rein, H.L., Bernstein, K.A.: Variants in the first methionine of RAD51C are homologous recombination proficient due to an alternative start site. DNA Repair 135: 103644, 2024.
196 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.
f3 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.
193 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.
155 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.
236 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.
16b 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.
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