JUL 31, 2018 5:45 PM PDT

Protein Regulation of DNA Replication in Cancer Cells - A New Early Target for Broad Therapeutics?

WRITTEN BY: Mauri Brueggeman

Researchers have been examining the loss of control over the DNA replication and cell proliferation process since it was connected to the development of cancer.  One of the most well-known and common traits of the disease in all types of cancer diagnoses is this this uncontrolled cellular replication and growth. 

In healthy cells, this process is carefully regulated and controlled through pathways and cellular checkpoints.  In a Nature Communications article published July 17, 2018, researchers identified a replication initiation determinant protein (RepID) that regulates replication through association of other proteins, drawing them directly to chromatin sites for replication initiation.  One of these proteins is a Culling-RING E3 ubiquitin ligase (CRL) which one of many CRLs.  CRL4 is recruited by RepID to chromatin in the very early stages of mitosis (cell cycle) prior to replication.  CRL4 acts to degrade CDT1, a protein that promotes replication at the appropriate time in the cell cycle.  Loss of CDT1 is the switch that tells a cell to only begin the DNA replication cycle once.  In addition to CRLs, a complex called SCF is also part of the cell cycle progression in mammals.  It, too, can facilitate degradation of chromatin proteins involved in regulation of mitosis and DNA replication later in the cell cycle (the S-phase).

In cases of RepID loss of expression or function, turning off that CDT1 switch is up to the SCF complex later in the cell cycle.  However, because the degradation was originated after DNA replication began, the cell re-replicated its DNA because there were higher levels of CDT1 associated with the chromatin.

Part of the SCF complex is a protein called SKP2.  This group of researchers treated the depleted RepID cancer cell cultures with a drug that inhibits SKP2, known as SZL-P1-41.  Their findings indicated that cells expressing intact RepID were not affected by the SKP2 inhibitor but cells with no RepID showed high sensitivity to SKP2 inhibition. The RepID knockout cells entered apoptosis and there were no surviving colonies in cell culture.  The researchers conclude that, “RepID expression levels might modulate the sensitivity of cancer cells to cullin-targeting drugs.”

Sources: Nature Communications, National Cancer Institute,

About the Author
  • Mauri S. Brueggeman is a Medical Laboratory Scientist and Educator with a background in Cytogenetics and a Masters in Education from the University of Minnesota. She has worked in the clinical laboratory, taught at the University of Minnesota, and been in post secondary healthcare education administration. She is passionate about advances and leadership in science, medicine, and education.
You May Also Like
JUN 24, 2021
Clinical & Molecular DX
Test Lets Cancer Patients Track Whether Their Treatment Is Working in Real Time
JUN 24, 2021
Test Lets Cancer Patients Track Whether Their Treatment Is Working in Real Time
Researchers from Singapore have created the ExoSCOPE, the world’s first blood test for tracking whether or not a p ...
JUN 21, 2021
Cancer
Analyzing breast implant topography and associated immune responses
JUN 21, 2021
Analyzing breast implant topography and associated immune responses
In an effort to understand how breast implants influence the immune system, researchers from MIT have led an analysis to ...
JUN 23, 2021
Cancer
Military universal health system boasts higher survival rates for colon cancer patients
JUN 23, 2021
Military universal health system boasts higher survival rates for colon cancer patients
New results published in the American Association for Cancer Research journal Cancer Epidemiology, Biomarkers & Prev ...
AUG 17, 2021
Clinical & Molecular DX
Delays in Breast Cancer Diagnoses Among Black Women
AUG 17, 2021
Delays in Breast Cancer Diagnoses Among Black Women
Thanks to breakthrough diagnostic technologies, we can now catch the early warning signs of breast cancer much faster th ...
OCT 07, 2021
Cell & Molecular Biology
Color-Changing Slides Improve Accuracy in Cancer Diagnosis
OCT 07, 2021
Color-Changing Slides Improve Accuracy in Cancer Diagnosis
When cancer is diagnosed, a sample has to be taken from a patient, treated, and analyzed. Researchers have now modified ...
OCT 18, 2021
Cancer
The History of Immunotherapy: Toxins, Targets & T Cells
OCT 18, 2021
The History of Immunotherapy: Toxins, Targets & T Cells
Cancer immunotherapy, a treatment that directly enhances a patient’s immune system, is typically perceived as a mo ...
Loading Comments...