# Ins and Outs of Abscission Checkpoint Signaling: Molecular Mechanisms Safeguarding Abscission

> **NIH NIH R35** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $149,558

## Abstract

PROJECT SUMMARY
The goal of this administrative supplement is to request funds for a state-of-the-art isothermal calorimeter for
measuring the thermodynamics of protein-protein and protein-small molecule interactions of proteins that are
critical for supporting cytokinetic abscission for R35GM150519. Cytokinetic abscission is the physical separation
of daughter cells that concludes mitosis. Premature abscission in the presence of incompletely segregated
chromosomes can result in chromosome breaks that give rise to DNA damage and micronuclei which are
hallmarks of cancer. To ensure that the onset of cytokinetic abscission is synchronized with the completion of
upstream mitotic events, cells maintain a cell cycle checkpoint known as the abscission checkpoint. Cells arrest
abscission in the presence of mitotic errors such as trapped DNA in the intercellular bridge, mis formed nuclear
pores, under-replicated DNA, and tension at the intercellular bridge. In this proposal we take an innovative
multidisciplinary approach that combines structure function studies with cell-based assays to address major
outstanding questions underlying abscission checkpoint regulation, including how cells sense checkpoint
triggers, and how protective activities are coupled with abscission. In Focus 1, we will use a structure-function
approach to understand the mechanism whereby the ESCRT abscission machinery recruits and triggers novel
cellular autophagy pathways. In Focus 2 we will examine how the metabolic status of a cell can lead to post-
translational modification of abscission checkpoint proteins to alter the fidelity of abscission, providing the first
direct links between glucose metabolism and abscission checkpoint function. Taken together, this work will
provide essential mechanistic, molecular-level insight into how cells promote faithful abscission, how the
mistakes in abscission can lead to the development of cancer, and ultimately, suggest therapeutic strategies for
combatting cancer cell proliferation.

## Key facts

- **NIH application ID:** 11037164
- **Project number:** 3R35GM150519-01S1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** DAWN WENZEL
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $149,558
- **Award type:** 3
- **Project period:** 2023-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11037164

## Citation

> US National Institutes of Health, RePORTER application 11037164, Ins and Outs of Abscission Checkpoint Signaling: Molecular Mechanisms Safeguarding Abscission (3R35GM150519-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11037164. Licensed CC0.

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