Related Experiment Video
Updated: Jan 17, 2026
12:02
Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
28.3K
A conserved Hsp70 phosphorylation regulates cell cycle progression after DNA damage
Thomas Moss1,2, Alexandra Wooldredge1,2, Koustav Bhakta1,2
1G.W. Hooper foundation, University of California at San Francisco, San Francisco, USA.
Biorxiv : the Preprint Server for Biology
|September 15, 2025
Summary
Heat shock protein 70 (Hsp70) phosphorylation at T495 occurs endogenously during DNA damage. This conserved modification regulates cell cycle progression and delays cell division, revealing fundamental cell biology insights.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Heat shock protein 70 (Hsp70) functions as a molecular chaperone.
- Post-translational modifications regulate Hsp70 activity.
- Pathogen kinases can target Hsp70 for inhibition.
Purpose of the Study:
- To investigate the endogenous phosphorylation of Hsp70 at T495 in human cells.
- To understand the role of Hsp70 phosphorylation in response to DNA damage.
- To elucidate the mechanism by which Hsp70 phosphorylation affects cell cycle progression.
Main Methods:
- Investigated endogenous Hsp70 phosphorylation in human cells using mass spectrometry.
- Utilized yeast models with phosphomimetic and phosphonull Hsp70 variants.
- Performed biochemical assays to analyze Hsp70 conformation and substrate binding.
Main Results:
- Hsp70 phosphorylation at T495 occurs endogenously in human cells during DNA damage, especially when base excision repair is stressed.
- This modification is cell cycle-dependent.
- In yeast, Hsp70 variants mimicking or lacking phosphorylation at T495 disrupt G1/S cell cycle progression under normal and DNA-damaging conditions.
- The T495E mutation results in an open-like Hsp70 conformation without impeding substrate binding.
Conclusions:
- Dynamic Hsp70 phosphorylation at T495 is a conserved mechanism regulating the G1/S transition.
- Hsp70 phosphorylation delays cell cycle progression in response to DNA damage.
- Insights from pathogen-host interactions can reveal fundamental principles of cell biology.
Related Concept Videos
02:36DNA Damage can Stall the Cell Cycle
10.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.0K
02:36DNA Damage Can Stall the Cell Cycle
3.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.0K
02:34Inhibition of Cdk Activity
5.5K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K
01:23Negative Regulator Molecules
38.3K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.3K
01:28The Cell Cycle Control System
5.4K
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
5.4K
02:11The Cell Cycle Control System
13.9K
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
13.9K