Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Mayo Clinic Researchers Identify Role of Cul4 Molecule in Genome Instability and Cancer

Published: Monday, November 11, 2013
Last Updated: Monday, November 11, 2013
Bookmark and Share
Cul4 helps to deposit DNA-packaging histone proteins onto DNA, an integral step to help compact the genetic code.

When DNA isn't packaged correctly, it can lead to the genomic instability characteristic of many forms of cancer. The research is published in the Nov. 7 issue of the journal Cell. The results explain on a molecular level how Cul4 enables the handoff of histones from the proteins escorting them from their birthplace in the cell to their workplace on the DNA, where they can begin wrapping DNA up into tidy units called nucleosomes.

"We suggest that cancer cells may have evolved a mechanism to disrupt proper nucleosome assembly by altering Cul4 and other factors, which in turn could affect the stability of the genome and promote the formation of tumors," says senior study author Zhiguo Zhang, Ph.D., a molecular biologist at Mayo Clinic.

To protect the integrity of the genome, DNA is packaged tightly, first around spools of histone to form nucleosomes, then stacked on top of each other to form chromatin and finally looped and coiled to form chromosomes. Depending on whether and how histones interact with a given genetic sequence, the DNA is either closed up tightly within this package or lies open so that the underlying genes can be read and become active.

Researchers have long known that special proteins — called histone chaperones — escort histones around the cell, but how they finally let go of the histones to deposit them onto DNA was unclear.

Dr. Zhang wondered if Cul4, which is altered in a number of human cancers, including breast cancer, squamous cell carcinomas, adrenocortical carcinomas, and malignant mesotheliomas, might be involved. So he and his colleagues developed a series of cellular assays in yeast and in human cells to investigate the role of Cul4 in nucleosome assembly.

They found that Cul4 modifies the chemical entities on the surface of the histones, weakening the interaction between them and the histone chaperones charged with their care. They noticed that the same observations held true in the yeast indicating that the role of Cul4 in nucleosome assembly and genome stability is likely conserved between yeast and human cells.

"We uncovered a novel molecular mechanism whereby Cul4 regulates nucleosome assembly," says Dr. Zhang. "Our finding underscores the fact that proper regulation of the nucleosome assembly pathway is a key step in maintaining genome stability and epigenetic information."


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Reprogramming Cancer Cells
Researchers on Mayo Clinic’s Florida campus have discovered a way to potentially reprogram cancer cells back to normalcy.
Wednesday, August 26, 2015
Mayo, Baylor Collaborate
They aim to study genomic links to drug metabolism and other interactions which could be used to provide more tailored patient care.
Friday, May 15, 2015
First Steps in Formation of Pancreatic Cancer Identified
Researchers at Mayo Clinic’s campus in Jacksonville say they have identified first steps in the origin of pancreatic cancer and that their findings suggest preventive strategies to explore.
Tuesday, November 11, 2014
Virotherapy Shows Promise Against Multiple Myeloma
A Mayo Clinic proof of principle clinical trial, demonstrated that virotherapy, destroying cancer with a virus that infects and kills cancer cells but spares normal tissues, can be effective against multiple myeloma.
Friday, May 16, 2014
Mayo Florida Receives $5M for Individualized Medicine Clinic
The donation from Florida residents Cecilia and Dan Carmichael will accelerate translation of research to patient care.
Wednesday, August 21, 2013
Mayo Clinic to Collaborate with Indian Science Leaders
The collaboration will cover areas such as drug, device and biomarker studies relating to heart disease, chemical biology, applied genomics and innovations in metabolomics.
Wednesday, October 19, 2011
TGen-Mayo Clinic Study Discovers Role of DNA Methylation in Multiple Myeloma
Report finds development of multiple myeloma is tied to ‘hypomethylation’.
Friday, October 01, 2010
Discovery Suggests Location of Genes for Breast Density, a Strong Risk Factor for Breast Cancer
Researchers at Mayo Clinic and H. Lee Moffitt Cancer Centers have identified a region on chromosome 5p that is associated with dense breast tissue.
Friday, September 07, 2007
Reactivating a Critical Gene Lost in Kidney Cancer Reduces Tumor Growth
Researchers have found that a key gene which is often silenced in clear cell renal cell carcinoma has stopped the tumor growth when restored in human kidney cancer cells.
Monday, August 20, 2007
Mayo Clinic Collaboration Discovers Protein Amplifies DNA Injury Signals
Protein MDC1 amplifies weak DNA injury signals so genetic repair can begin.
Friday, January 27, 2006
Researcher Discover Why Some DNA Repair Fails
This discovery may lead to ways of fixing the process to avoid Huntington's disease and some types of colon cancer.
Wednesday, October 05, 2005
Scientific News
Improving Regenerative Medicine
Lab-created stem cells may lack key characteristics, UCLA research finds.
Tick Genome Reveals Secrets of a Successful Bloodsucker
NIH has announced that decipher the genome of the blacklegged tick which could lead to new tick control methods.
"Dark Side" of the Transcriptome
New approach to quantifying gene "read-outs" reveals important variations in protein synthesis and has implications for understanding neurodegenerative diseases.
Individuals' Medical Histories Predicted by their Noncoding Genomes
Researchers have found that analyzing mutations in regions of the genome that control genes can predict medical conditions such as hypertension, narcolepsy and heart problems.
New Source of Mutations in Cancer
Recently, a new mutation signature found in cancer cells was suspected to have been created by a family of enzymes found in human cells called the APOBEC3 family.
Advancing Synthetic Biology
Living systems rely on a dizzying variety of chemical reactions essential to development and survival. Most of these involve a specialized class of protein molecules — the enzymes.
Biosensors on Demand
New strategy results in custom "designer proteins" for sensing a variety of molecules.
Unique Mechanism for a High-Risk Leukemia
Researchers uncovered the aberrant mechanism underlying a notoriously treatment-resistant acute lymphoblastic leukemia subtype; findings offer lessons for understanding all cancers.
Genetically Mapping the Most Lethal E.Coli Strains
New approach could lead to fewer deaths, and new treatments.
Pumpjack" Mechanism for Splitting and Copying DNA
High-resolution structural details of cells' DNA-replicating proteins offer new insight into how these molecular machines function
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!