# Understanding Cell Division

> **NIH NIH R35** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2020 · $49,450

## Abstract

Abstract
Cell division requires a complex network of dozens of pathways whose interactions drive key transitions. One of
the most critical is the transition from metaphase to anaphase and mitotic exit. The Anaphase-Promoting
Complex/Cyclosome (APC/C), an E3 ubiquitin ligase, comprises the central target node of this critical decision
point. APC/C activity is sensitive to chromosome congression to the metaphase plate. At metaphase, the APC/C
ubiquitylates target mitotic regulators for destruction in the proteasome and induction of chromatid separation
and mitotic exit. While regulatory pathways for the APC/C have been identified, complete understanding of how
it is tuned to program the metaphase-anaphase transition after chromosome alignment remains unclear. Recent
work has implicated the Spindle and Kinetochore Associated (Ska) protein complex as a key element. The
studies proposed will clarify the molecular mechanisms by which Ska collaborates with and controls other mitotic
regulators, particularly protein phosphatases, governing the temporal and spatial activation of the APC/C to drive
the metaphase-anaphase transition. Metaphase, itself, is generally brief, but the Gorbsky laboratory discovered
that delays, even short ones, can cause partial or complete chromatid separation, a phenomenon termed
“cohesion fatigue.” Cohesion fatigue may be remarkably common as a source of both numerical aneuploidy and
large chromosome deletions, duplications and translocations, particularly in cells transformed by activated
oncogenes and the loss of tumor suppressors. The Gorbsky laboratory is taking a broad approach to study all
potential inputs that contribute to cohesion fatigue. The laboratory is also mapping the short term and long term
consequences of cohesion fatigue to determine how it promotes chromosome missegregation and damage.
Finally, complete understanding of cell division and its transitions can only occur if all components and regulators
of the process are identified. While the mitotic parts list is already large, continued reports of new components
indicate that it is not yet complete in vertebrates. Using bioinformatic guidance that has proven highly effective,
the Gorbsky lab is testing candidate mitotic regulators and characterizing their functions in cell division in normal
and transformed cells.

## Key facts

- **NIH application ID:** 10133790
- **Project number:** 3R35GM126980-03S1
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** GARY J. GORBSKY
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $49,450
- **Award type:** 3
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133790

## Citation

> US National Institutes of Health, RePORTER application 10133790, Understanding Cell Division (3R35GM126980-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133790. Licensed CC0.

---

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