Paula Bubulya (Advisor), Mark Mamrack (Committee Member), Mill Miller (Committee Member)
Master of Science (MS)
Mitosis is an intricate process that is monitored by multiple cell cycle regulator proteins. Errors in mitotic regulation have been linked to many types of cancer. Recently, evidence suggests an indirect regulation of mitosis by nuclear speckle proteins. Nuclear speckles are one of the multiple compartments found in the mammalian cell nucleus. They serve as assembly compartments for premRNA processing factors. Mass spectrometry analysis of purified nuclear speckles revealed 33 novel proteins including Son and TRAP150. The aim of my study was to determine how Son and TRAP150 can directly or indirectly impact mitosis. We and others recently reported that Son is required to maintain cell proliferation, as its depletion results in growth arrest in metaphase. We hypothesized that Son is required for the assembly of important mitotic structures such as the mitotic spindle and kinetochores. My results showed elongated and disorganized mitotic spindles in Son-depleted cells. In addition, my studies showed a novel localization pattern for Son in cytoplasmic foci following microtubule destabilization at metaphase. Son is important in the alternative splicing of transcripts that encode cell cycle regulators (Sharma et al., 2011). Therefore the mitotic defects seen are most likely explained by alternative splicing defects that occur after Son depletion. In addition, preliminary evidence from the Bubulya lab showed the mitotic defects in TRAP-150 depleted cells suggesting a role for TRAP150 in mitosis. Given that TRAP150 did not colocalize with mitotic structures during mitosis, we hypothesized that TRAP150 depletion alters mitosis by altering the transcripts of mitotic regulators. My results indicated that TRAP150 is important in controlling abundance of transcripts that encode mitotic regulators.
Department or Program
Department of Biological Sciences
Year Degree Awarded
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