# Dynamic Events at the Nuclear Envelope during Mitosis and Interphase

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $356,895

## Abstract

PROJECT ABSTRACT
The nuclear envelope encloses the nucleus and establishes a critical protective barrier around genomic DNA.
Proteins embedded in and associated with the two membrane bilayers of the nuclear envelope play crucial roles
in mediating chromatin organization, nuclear positioning, and connections to the cytoskeletal network. There is
growing appreciation that disruption of nuclear envelope integrity is linked to multiple aging-associated diseases
and contributes to genomic instability in cancer. Upon each cell division in mammalian cells, the nucleus is
dismantled and reformed. Scrutiny of nuclear envelope assembly has revealed the remarkable feature that two
distinct domains are present at the nascent nuclear envelope. Core regions at the center of each face of the
anaphase chromatin disk are a site of microtubule remodeling, and non-core regions at the disk periphery are a
site of rapid nuclear pore formation. This specialization facilitates quick, coordinated enclosure of chromatin.
Progression to interphase nuclear architecture involves elimination of the distinction between these regions and
further expansion of membrane. Completion of nuclear assembly, however, does not mean that the nuclear
envelope is static. Indeed, emerging evidence supports the notion that continuous adaptations must take place
at the nuclear envelope to maintain nuclear envelope structure and, in some cases, to sculpt new architectural
features. Using approaches ranging from timelapse microscopy to proximity labeling, this proposal seeks to
address fundamental questions about how the nuclear envelope is formed and how its organization and topology
are maintained. Toward this end, the first aim is to determine molecular pathways that underlie dynamic
organization of the nascent nuclear envelope. This aim will focus on testing roles of the inner nuclear membrane
protein LEM2, defining motifs that direct core/non-core regional targeting, and investigating how dissolution of
the core region is accomplished. Added insight will be gained by examining how the nuclear envelope forms at
micronuclei, which arise from mis-segregated chromosomes; in particular, we will investigate how a fragile
nuclear envelope forms in a subpopulation of micronuclei. The second aim is to elucidate the role of LEM2 in
dynamic events at the interphase nuclear envelope and learn how these are altered in disease-associated alleles
of LEM2. This aim takes advantage of a system in which nuclear membrane deformation can be induced to test
mechanisms that contribute to the resilience of nuclear envelope architecture. Results reported in the literature,
as well as our observations, implicate LEM2 in responding to these perturbations. These complementary aims
will yield a deeper understanding of nuclear envelope formation and reveal pathways that play critical roles in
nuclear architecture, as well as probe how they go awry at micronuclei and are disrupted in human disease.

## Key facts

- **NIH application ID:** 10802853
- **Project number:** 2R01GM131052-05A1
- **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:** 2024
- **Award amount:** $356,895
- **Award type:** 2
- **Project period:** 2019-02-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802853

## Citation

> US National Institutes of Health, RePORTER application 10802853, Dynamic Events at the Nuclear Envelope during Mitosis and Interphase (2R01GM131052-05A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10802853. Licensed CC0.

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