Related Experiment Video

Updated: May 16, 2026

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

DNA damage-specific control of cell death by cryptochrome in p53-mutant ras-transformed cells

Jin Hyup Lee1, Shobhan Gaddameedhi, Nuri Ozturk

  • 1Department of Biochemistry and Biophysics, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, USA.

Cancer Research
|November 15, 2012
PubMed

Insights

Cryptochromes (Cry1 and Cry2) influence tumor suppression and apoptosis. Cry1/Cry2 mutations enhance apoptosis induced by UV and oxaliplatin via Egr1, but not doxorubicin via E2F1.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Circadian rhythm in mice is regulated by cryptochromes (Cry1 and Cry2).
  • Cry1/Cry2 mutations delay tumor formation in p53-null mice and increase apoptosis sensitivity in Ras-transformed fibroblasts.
  • The role of cryptochromes in genotoxic agent-induced apoptosis requires further investigation.

Purpose of the Study:

  • To investigate the impact of Cry1 and Cry2 mutations on apoptosis induced by various genotoxic agents.
  • To elucidate the specific pathways and transcription factors involved in cryptochrome-mediated apoptosis.

Main Methods:

  • Utilized p53-null and Cry-null mouse skin fibroblasts.
  • Administered genotoxic agents including ultraviolet (UV) radiation, oxaliplatin, and doxorubicin.
  • Assessed apoptosis induction and the involvement of p73, Egr1, and E2F1.

Main Results:

  • UV, oxaliplatin, and doxorubicin induced apoptosis by upregulating p73.
  • Cry1/Cry2 double mutation enhanced UV and oxaliplatin-induced p73 upregulation mediated by Egr1.
  • Doxorubicin-induced p73 upregulation, mediated by E2F1, was not enhanced by Cry1/Cry2 mutations.
  • Egr1 downregulation reduced oxaliplatin-induced apoptosis, while E2F1 downregulation reduced doxorubicin-induced apoptosis.

Conclusions:

  • Cryptochromes play distinct roles in apoptosis induced by UV mimetic (oxaliplatin) and radiomimetic (doxorubicin) agents.
  • Cry1/Cry2 mutations specifically enhance apoptosis mediated by the Egr1 pathway in response to oxaliplatin.
  • Findings highlight the differential involvement of cryptochromes in genotoxic stress response pathways.

More Related Videos

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

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...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

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.
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...