# Cellular Events Downstream of Mitotic Errors

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $343,125

## Abstract

PROJECT SUMMARY
In animal cells, nuclear structure is completely dismantled during the process of mitosis. Although chromosomes
are concomitantly remodeled into compact, protective structures, various sources of error can put genome
stability at risk at this time of cell division. Chromosome division itself can be a time of genome destabilizing
errors, if the spindle assembly checkpoint fails to ensure that chromosome alignment is complete prior to their
segregation. In some cases, events in the previous cell cycle, such as incomplete DNA replication, put the
genome in jeopardy at mitosis. In other cases, mis-coordination of events in late mitosis gives rise to DNA
damage. Events downstream of these potential errors thus play an integral role in maintaining genome stability.
A growing body of knowledge about the rapid steps of nuclear assembly and an appreciation for the importance
of genome surveillance in newly-formed nuclei provide a foundation for the proposed research designed to
address how cells cope with mitotic errors. The research proposed is centered on conceptually innovative
hypotheses and seeks to make novel inroads into the inter-connections between nuclear assembly, genome
surveillance, and cytokinesis. Building on the new observation that the nuclear envelope at lagging
chromosomes has a specific set of constituent proteins, our first aim is to define how the nuclear envelope differs
at mis-segregated chromosomes, testing the hypothesis that these changes alter membrane sealing. The impact
that this distinctive nuclear envelope domain has on nuclear integrity and the frequency with which mis-
segregating chromosomes re-integrate into the nucleus will be determined by live-imaging. We will also
interrogate the role of the kinase Aurora B in regulating regional differences at the NE of lagging chromosomes.
In cases where the lagging chromosome separates from the main nucleus, our results will also lend insight into
why resulting micronuclei have attributes that escalate DNA damage and instigate innate immune signaling. The
second aim is focused on mechanisms involved in genome surveillance after mitosis. To gain unique perspective
on this process, we will pursue the roles of Nup153 and Nup50 in targeting the DNA damage response factor
53BP1 to surveillance foci. Finally, we will determine what activates the abscission checkpoint, a regulatory event
downstream of mitosis that halts the final step of cell division. Having observed a robust connection between
loss of Nup153 function and the abscission checkpoint, we hypothesize that this is due to the dual roles of
Nup153 in nuclear formation and genomic surveillance. More broadly, we will test the hypothesis prompted by
this paradigm: that loss of nuclear integrity --and the damage to DNA that ensues-- are monitored by the
abscission checkpoint and become a particularly potent signal when genome surveillance mechanisms are
compromised. The results obtained will bring significant new ...

## Key facts

- **NIH application ID:** 9870940
- **Project number:** 5R01GM131052-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** KATHARINE S ULLMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,125
- **Award type:** 5
- **Project period:** 2019-02-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870940

## Citation

> US National Institutes of Health, RePORTER application 9870940, Cellular Events Downstream of Mitotic Errors (5R01GM131052-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9870940. Licensed CC0.

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