Medindia LOGIN REGISTER
Medindia
Advertisement

Cancer Development Begins with Premature Cells

by Preethi Sivaswaamy Mohana on March 1, 2018 at 12:51 PM
Cancer Development Begins with Premature Cells

New mutations by advanced entry of the genome into the replication phase lead to the origin of cancers as well as the development of its resistance to treatments, according to a new study by biologists from the University of Geneva (UNIGE), Switzerland. These genes induce cells to start replicating their DNA prematurely during the cell cycle and the abnormal cell division causes a tumor to develop. The results of the study are published in the journal Nature.

When a cell divides into two daughter cells, it must replicate its entire genome and transcribe part of it to make new proteins. Cell division is notably regulated by specific genes, including the proto-oncogenes Cyclin E and Myc. Their overexpression or mutation into oncogenes, following exposure of cells to a carcinogen for example, leads to uncontrolled proliferation of cells and promotes the formation of cancer. "We wanted to understand why numerous mutations accumulate in cells with activated oncogenes", explains Thanos Halazonetis, Professor at the Department of Molecular Biology of the UNIGE Faculty of Science.

Advertisement


Replication must begin between two genes

In order to replicate its entire DNA, that is to say nearly 6.4 billion pairs of nucleotides in just a few hours, the cell organizes the preparation of this process at thousands of sites on each chromosome simultaneously. The position and spacing of these sites, called 'replication origins', must be controlled to ensure that replication takes place in a smooth and efficient way.
Advertisement

The UNIGE scientists have developed a method to identify the origins of replication on all chromosomes. This consists of isolating and sequencing the newly synthesized DNA from cells that have just entered the replication phase, in order to map on the genome the sites where replication has begun. This method, specifically developed for human cells, offers high degrees of sensitivity and resolution.

"Initially, the cell identifies all potential replication origins with a molecular marker. We have discovered that in normal cells, the aberrant replication origins are subsequently eliminated. This is the case for those that are located inside a gene, whereas they should be outside the genes so that the integral message of each gene is preserved", explains Morgane Macheret, a scientist at the Department of Molecular Biology at UNIGE and first author of the article.

When the cells skip steps

The activation of the oncogenes Cyclin E or Myc, on the other hand, induces the cells to begin replication of their DNA prematurely, without having had time to eliminate all the replication origins present in the genes. "The replication and transcription machineries are therefore active simultaneously on genes carrying a replication origin, which causes conflicts. Our analyses show that these conflicts induce DNA breakdowns, chromosomal rearrangements and, therefore, mutations", says Thanos Halazonetis.

Do these results explain the genomic instability present in different types of cancers? In order to answer this question, the biologists have studied an array of more than 500'000 chromosomal rearrangements already characterized in a wide range of tumors.

"We observed that these chromosomal defects are particularly common in the conflict zones we described. We hope that the discovery of the mechanism that partly or totally explains the genesis of this genomic instability will eventually lead to the development of new therapeutic strategies", concludes Morgane Macheret.



Source: Eurekalert
Font : A-A+

Advertisement

Advertisement
Advertisement

Recommended Readings

Latest Cancer News

Blood Test for Early Detection of Pancreatic Cancer
The blood test pinpointed 13 proteins capable of distinguishing between early and late stages of pancreatic cancer.
Nutrients in Beef and Dairy Promote Cancer Immunotherapy
A fatty acid present in dairy products, beef, and lamb called trans-vaccenic acid enhances immune cells' capacity to combat cancers.
Combination Therapy Holds Promise for Brain Tumor in Children
Trametinib plus dabrafenib combined therapy demonstrated a clear therapeutic benefit in children with BRAF-mutated low- and high-grade gliomas.
Urban Environments Fuel Higher Breast Cancer Rates
Examining breast cancer occurrence and stages reveals disparities in urban versus rural rates, influenced by environmental conditions and the stage of the disease.
DNA Repair Pathway Linked to Breast, Ovarian, and Prostate Cancers
Polymerases theta and delta assist in the development of new cancer drugs known as polymerase theta inhibitors, currently undergoing clinical trials.
View All
This site uses cookies to deliver our services.By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use  Ok, Got it. Close
×

Cancer Development Begins with Premature Cells Personalised Printable Document (PDF)

Please complete this form and we'll send you a personalised information that is requested

You may use this for your own reference or forward it to your friends.

Please use the information prudently. If you are not a medical doctor please remember to consult your healthcare provider as this information is not a substitute for professional advice.

Name *

Email Address *

Country *

Areas of Interests