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

> **NIH NIH R35** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $390,000

## Abstract

PROJECT SUMMARY:
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 have evolved 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:** 10913457
- **Project number:** 5R35GM150519-02
- **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:** $390,000
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913457

## Citation

> US National Institutes of Health, RePORTER application 10913457, Ins and Outs of Abscission Checkpoint Signaling: Molecular Mechanisms Safeguarding Abscission (5R35GM150519-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10913457. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*