# Mechanisms that coordinate cell size and mitotic entry

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2020 · $324,000

## Abstract

A wide variety of cell types delay cell cycle transitions until they reach a critical size threshold,
but the mechanisms that measure size and transmit this information to the core cell cycle
machinery are largely unknown. Conserved cell cycle regulators form two discrete populations
of large, multi-protein structures called “nodes” at the cortex of fission yeast cells. One
population of nodes contains the protein kinases Cdr2, Cdr1, and Wee1, which function in a
linear, genetically defined pathway to regulate mitotic entry. We discovered a second population
of nodes that contain Skb1, which inhibits mitotic entry by binding to Cdr1 and Wee1. Node
assembly is required for control of cell size at division, but we do not know the mechanisms of
assembly or signal transduction within nodes. We will address key open questions using
powerful genetic, biochemical, and quantitative imaging approaches. We will focus on the
fundamental process of cell cycle regulation, but our work has broad implications for spatial
control of signal transduction because higher-order clusters and node-like structures are
emerging as critical sites of signal transduction throughout cell biology. The specific aims of this
grant are to: (1) define the molecular mechanism by which Cdr2 organizes nodes and transmits
cell size signals, (2) test the hypothesis that node function and organization respond to
environmental changes, and (3) determine how Skb1 nodes inhibit mitotic entry by signaling to
Cdr2-Cdr1-Wee1 nodes. Successful completion of these goals will advance scientific knowledge
by identifying how protein clustering in nodes coordinates cell growth and division. Moreover,
the signaling mechanisms that we uncover will provide insights for how size controls the activity
of other biological systems.

## Key facts

- **NIH application ID:** 9850597
- **Project number:** 5R01GM099774-09
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** James B Moseley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $324,000
- **Award type:** 5
- **Project period:** 2012-02-06 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850597

## Citation

> US National Institutes of Health, RePORTER application 9850597, Mechanisms that coordinate cell size and mitotic entry (5R01GM099774-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9850597. Licensed CC0.

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