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CL Dissertation 041515.pdf (23.47 MB)

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Analysis of two factors, BARD1 and MYCBP, that stimulate DNA double strand break repair

Lee, Cindy
http://orcid.org/0000-0001-5448-8943
http://rave.ohiolink.edu/etdc/view?acc_num=osu1429262304

Abstract Details

2015, Doctor of Philosophy, Ohio State University, Molecular, Cellular and Developmental Biology.
Deleterious mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 are highly penetrant, resulting in a 50-80% lifetime risk of breast or ovarian cancer; however, known mutations only account for 20% of familial breast cancer cases. Previous studies revealed the correlation between function in DNA double strand break repair and pathogenicity in clinic, so our search for missing heritability is rooted in the BRCA pathways of DNA double strand break repair. Gene sequencing panels have identified a multitude of variants in BRCA1 that are of unknown clinical significance, some of which have been clarified by functional assays and clinical modeling. Similarly, we have analyzed 29 missense substitutions in BARD1, the interacting partner of BRCA1, for function in homology-directed repair, and mapped the non-functioning variants to 3-D structures in BARD1 that are likely crucial for tumor suppression. Using DNA double strand break repair pathways to build gene co-expression networks, we have identified a novel stimulator of DNA repair, MYCBP. Depletion of MYCBP abrogates both homologous and non-homologous repair of DNA double strand breaks; the significant impact on DNA double strand break repair stems from the role of MYCBP in stimulating transcription of the DNA repair factors BRCA1, RAD51, and 53BP1. That depletion of MYCBP also sensitizes cancer cells to DNA damage agents suggests a mode of targeted therapy in future studies. Our investigations of BARD1 and MYCBP have deepened the understanding of a known DNA repair factor and identified a novel stimulator of DNA repair, increasing the links between DNA repair and cancer.
Jeffrey Parvin, MD/PhD (Advisor)
Kun Huang, PhD (Committee Member)
Thomas Ludwig, PhD (Committee Member)
Amanda Toland, PhD (Committee Member)
108 p.
Bioinformatics; Molecular Biology
DNA repair; MYCBP; BARD1; breast cancer

Recommended Citations

Citations

  • Lee, C. (2015). Analysis of two factors, BARD1 and MYCBP, that stimulate DNA double strand break repair [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429262304

    APA Style (7th edition)

  • Lee, Cindy. Analysis of two factors, BARD1 and MYCBP, that stimulate DNA double strand break repair. 2015. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1429262304.

    MLA Style (8th edition)

  • Lee, Cindy. "Analysis of two factors, BARD1 and MYCBP, that stimulate DNA double strand break repair." Doctoral dissertation, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429262304

    Chicago Manual of Style (17th edition)

osu1429262304
211
© 2015, some rights reserved.Creative Commons License Analysis of two factors, BARD1 and MYCBP, that stimulate DNA double strand break repair by Cindy Lee is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by The Ohio State University and OhioLINK.