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Tangeman final thesis.pdf (2.06 MB)

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Regulation of BLM Nucleolar Localization

Tangeman, Larissa J.
http://rave.ohiolink.edu/etdc/view?acc_num=osu148347431702817

Abstract Details

2017, Master of Science, Ohio State University, Biomedical Sciences.
Defects in coordinated ribosomal RNA (rRNA) transcription in the nucleolus cause cellular and organismal growth deficiencies. Bloom’s syndrome, an autosomal recessive human disorder caused by mutated recQ-like helicase BLM, presents with growth defects suggestive of underlying defects in rRNA transcription. Our previous studies showed that BLM facilitates rRNA transcription and interacts with RNA polymerase I and topoisomerase I (TOP1) in the nucleolus. The mechanisms regulating localization of BLM to the nucleolus are unknown. In this study, we identify the TOP1-interaction region of BLM by co-immunoprecipitation of in vitro transcribed and translated BLM segments and show that this region includes the highly conserved nuclear localization sequence (NLS) of BLM. Biochemical and nucleolar co-localization studies using site-specific mutants show that two serines within the NLS (S1342 and S1345) are critical for nucleolar localization of BLM but do not affect the functional interaction of BLM with TOP1. Mutagenesis of both serines to aspartic acid (phospho-mimetic), but not alanine (phospho-dead), results in approximately 80% reduction in nucleolar localization of BLM while retaining the biochemical functions and nuclear localization of BLM. Our studies suggest a role for this region in regulating nucleolar localization of BLM via modification of the two serines within the NLS.
Joanna Groden, PhD (Advisor)
Jeffrey Parvin, MD, PhD (Committee Member)
73 p.
Biochemistry; Genetics; Molecular Biology
Regulation, BLM Nucleolar Localization

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Citations

  • Tangeman, L. J. (2017). Regulation of BLM Nucleolar Localization [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu148347431702817

    APA Style (7th edition)

  • Tangeman, Larissa. Regulation of BLM Nucleolar Localization. 2017. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu148347431702817.

    MLA Style (8th edition)

  • Tangeman, Larissa. "Regulation of BLM Nucleolar Localization." Master's thesis, Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu148347431702817

    Chicago Manual of Style (17th edition)

osu148347431702817
432
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This open access ETD is published by The Ohio State University and OhioLINK.