# Molecular Mechanisms of Cell Cycle Control

> **NIH NIH R35** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $452,453

## Abstract

ABSTRACT
Regulated progression through the cell division cycle is critical for cells to faithfully grow and divide. When cell
cycle control is disrupted, cells can acquire mutations or proliferate uncontrollably, and this can lead to the
development of diseases such as cancer. To ensure that cells replicate and divide accurately, multiple
overlapping mechanisms function to coordinate and order cell cycle events. The focus of my laboratory is to
understand how cell cycle-regulated transcription, phosphorylation and ubiquitin-mediated protein degradation
are integrated to generate a robust cell cycle-regulatory network. To accomplish this we take advantage of
high-throughput genetic approaches in budding yeast to uncover the systems-level consequences of
perturbing cell cycle-regulatory genes. In this proposal we will focus on three key unanswered questions. First,
how does phosphorylation of cell cycle-regulatory transcription factors (TFs) contribute to cell cycle control?
We will utilize genetic interaction screens with phosphodeficient TF alleles to elucidate the importance of
phosphorylation and test the hypothesis that TF phosphorylation is important to coordinate growth and energy
production with the cell cycle. Second, how do stress response pathways cooperate to regulate the cell cycle in
response to environmental stress? We will dissect the mechanism of crosstalk between conserved stress
response pathways and investigate the importance of this crosstalk for cell cycle arrest and survival in
response to distinct environmental stressors. Third, how do deubiquitinating enzymes (DUBs) regulate the
stabilities of cell cycle-regulatory proteins? We will utilize an approach that we developed for identifying DUB
substrates to investigate the in vivo functions of these enzymes and the mechanisms by which they control the
cell cycle. By answering these questions, we will develop a network-level view of how transcription and
proteolysis coordinate cell cycle events to ensure faithful cell division. Given the strong conservation between
the cell cycle-regulatory mechanisms in yeast and human cells, we anticipate this work will provide insight into
how disruptions in the cell cycle control network contribute to disease.

## Key facts

- **NIH application ID:** 9930722
- **Project number:** 1R35GM136280-01
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Jennifer A Benanti
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $452,453
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930722

## Citation

> US National Institutes of Health, RePORTER application 9930722, Molecular Mechanisms of Cell Cycle Control (1R35GM136280-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9930722. Licensed CC0.

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