Dissertation
Transcription factor specificity protein 1 regulates chromosome assembly and segregation during mitosis
Doctor of Philosophy (Ph.D.), Drexel University
Sep 2020
DOI:
https://doi.org/10.17918/00000270
Abstract
Aneuploidy is a ubiquitous feature of cancer that results from chromosome missegregation. Errorless segregation requires proper assembly of mitotic chromatin, a dynamic process that is incompletely understood. Despite their salient role directing interphase chromatin organization, little is known about how transcription factors mediate this process during mitosis. Here, we characterize a mitosis-specific role for transcription factor specificity protein 1 (Sp1) in mitotic chromosome segregation and assembly. Sp1 localizes to mitotic centromeres and auxin-induced rapid Sp1 degradation results in chromosome segregation errors, aberrant mitotic progression, and metaphase chromosome misalignment. These defects are driven by aberrant assembly of mitotic chromosomes. Sp1 degradation results in chromosome condensation defects through reduced condensin complex I localization. Sp1 is also required for the localization and activation of Aurora B kinase early in mitosis, which is essential for condensin complex I recruitment. Our results suggest that Sp1 protects genomic integrity during mitosis by promoting chromosome assembly.
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Details
- Title
- Transcription factor specificity protein 1 regulates chromosome assembly and segregation during mitosis
- Creators
- Samuel Flashner
- Contributors
- Jane Clifford (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xii, 176 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 991014695147404721