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Nup2 and a Newly Discovered Nuclear Pore Complex Protein, NupA, Function at Mitotic Chromatin Controlled by the NIMA Kinase

Markossian, Sarine W.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1306851345

Abstract Details

2011, Doctor of Philosophy, Ohio State University, Molecular Genetics.
In Aspergillus nidulans the mitotic NIMA kinase is required for the transition from G2 into mitosis. How NIMA regulates this process is not well understood. The nucleoporin Nup2 is of interest because it is essential and has a unique and conserved ability to transfer from nuclear pore complexes (NPCs) to chromatin specifically at mitosis. This unique transition suggests that Nup2 might play mitotic roles downstream of NIMA conserved from fungi to humans. We have determined that NIMA promotes Nup2 phosphorylation and relocation from NPCs onto chromatin. Affinity purifications followed by Mass spectroscopy identified a novel nucleoporin, NupA, which copurified with Nup2. NupA transfers from NPCs to mitotic chromatin and is also essential. Deletion analysis and heterokaryon rescue revealed that deletion of either does not cause major defects in nuclear transport but causes mitotic abnormalities that engage the spindle assembly checkpoint (SAC). We have also defined the essential function of NupA which is to tether Nup2 to both the NPC and mitotic chromatin where we propose Nup2 has a role in promoting efficient generation and function of the mitotic apparatus. In addition, Nup2 and NupA have dynamic locations within mitotic chromatin during different phases of mitosis. They are associated throughout chromatin at early prophase but move to locate at the periphery of the chromatin during the transition from anaphase to telophase. This movement at anaphase is likely functionally significant as deletion of either Nup2 or NupA causes defects in mitotic exit into G1. Hence, Nup2 and NupA may have dual roles in mitosis, the first being during early mitosis, defects in which activates the SAC, and the latter in mitotic exit and early G1. Because Nup2 co- purifies with importins α and β, we propose that both roles might be linked to proper localizations and functions of importins α and β during metaphase and mitotic exit. These studies collectively demonstrate that Nup2 and the newly discovered NupA have important functions during mitosis that are controlled by NIMA.
Stephen A. Osmani, PhD (Advisor)
Anita K. Hopper, PhD (Committee Member)
Iris Meier, PhD (Committee Member)
Harold A. Fisk, PhD (Committee Member)
Cellular Biology; Molecular Biology
NPC; Nup2; NupA; Nucleoporin; Mitosis; NIMA; Aspergillus nidulans

Recommended Citations

Citations

  • Markossian, S. W. (2011). Nup2 and a Newly Discovered Nuclear Pore Complex Protein, NupA, Function at Mitotic Chromatin Controlled by the NIMA Kinase [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1306851345

    APA Style (7th edition)

  • Markossian, Sarine. Nup2 and a Newly Discovered Nuclear Pore Complex Protein, NupA, Function at Mitotic Chromatin Controlled by the NIMA Kinase. 2011. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1306851345.

    MLA Style (8th edition)

  • Markossian, Sarine. "Nup2 and a Newly Discovered Nuclear Pore Complex Protein, NupA, Function at Mitotic Chromatin Controlled by the NIMA Kinase." Doctoral dissertation, Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1306851345

    Chicago Manual of Style (17th edition)

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© 2011, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.