AUG 21, 2017 2:58 PM PDT

Faulty Genetic Replication can Cause Problems for Future Generations

WRITTEN BY: Carmen Leitch

Our body is in a constant state of renewal as old cells divide into new ones. Cell division has to be carefully controlled during development and has to be constantly regulated to guard against the growth of tumors. Every time cells divide, our genetic material has to be duplicated, and errors in that process can have dire consequences. Dysfunction in DNA replication has been associated with cancer and can lead to new mutations in the genome. Researchers have now linked impairments in DNA replication to changes in the entire genome -- epigenetic changes that can then be passed down to up to five generations.

This work, by researchers at the Centre for Genomic Regulation (CRG), Josep Carreras Leukaemia Research Institute (IJC) and at The Institute for Health Science Research Germans Trias i Pujol (IGTP), has been reported in Science Advances and is outlined in the video. The scientists used Caenorhabditis elegans, a worm, as the model for this work. Impairments in DNA replication are illustrated in the video.

This work suggests that people might have different gene expression simply because they have inherited different epigenetic markers. 

The investigators looked for the mechanism that was driving these genome-wide changes. The problem started with genome replication and was traced to the heterochromatin complex (learn more about it from the video below).

"For the correct function of cells and ultimately the health of the organism, it is important to keep certain genes active and others silenced. Inside cells, there are DNA-protein complexes called heterochromatin that prevent genes from becoming activated when they should not be,” explained study co-author Tanya Vavouri, a CRG alumna currently group leader at IJC and IGTP.

“Initially, we noticed that a gene artificially inserted into the worm genome and normally silenced by heterochromatin was activated in animals that carried mutations in proteins involved in the copying of DNA. We found that this was caused by loss of heterochromatin and that other genes also silenced by heterochromatin were activated too,” she added.

Adult C. elegans worms can be seen with embryos inside them. CREDIT Adam Klosin, CRG

These errors turned out to be heritable. “Unexpectedly, the gene was inappropriately activated for five generations in animals that did not carry the mutation in DNA replication but had ancestors that did," Vavouri said.

"Our results show that impaired DNA replication not only causes genetic alterations but also genome-wide epigenetic changes that can be stably inherited," noted senior author Ben Lehner.

Scientists have been trying to determine the degree to which epigenetic modifications might be passed onto future generations. This research team is continuing to investigate. They have also found that temperature can cause gene expression changes that are transmitted between generations.

"We hope that our work will change the way people think about the impact of replication stress during tumorigenesis and embryonic development as well as about inter-generational inheritance," he concluded.

 

Sources: AAAS/Eurekalert! Via Center for Genomic Regulation, Science Advances

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
JAN 04, 2020
Immunology
JAN 04, 2020
Why Do Skincare Products Sometimes Cause Rashes?
Chemicals commonly found in skincare products are intended to avoid interactions with the part of the immune system responsible for triggering allergic inf...
JAN 08, 2020
Cell & Molecular Biology
JAN 08, 2020
In a First, Scientists Generate Early Human Immune Cells in the Lab
Now we know more about the early stages of the human immune system....
JAN 15, 2020
Cell & Molecular Biology
JAN 15, 2020
Cell Division Research Reveals More About a Protein That's Elevated in Cancer
Cell division is a carefully regulated process, cancer is the result when it gets out of control....
JAN 20, 2020
Genetics & Genomics
JAN 20, 2020
Braveheart RNA Structure is Revealed For the First Time
Protein-coding genes only make up a small part of the genome. Much of the rest may contain long, non-coding RNA sequences....
JAN 20, 2020
Neuroscience
JAN 20, 2020
Ovarian Cancer Protein Accelerates Alzheimer's Neurodegeneration
Around 21,000 people in the US are diagnosed with ovarian cancer every year, while an estimated 5.8 million Americans have Alzheimer’s. Now, research...
FEB 11, 2020
Neuroscience
FEB 11, 2020
Soybean oil Causes Genetic Changes in Mouse Brain
Source: Hypothalmus and limic system   Soybean oil is used for cooking fast food, in packaged products, and to feed livestock, making it the most wide...
Loading Comments...