To survive, thrive and reproduce successfully, organisms rely on a high level of genetic stability. Mutagenic agents, which can threaten the integrity of the genetic code by causing mutations in DNA, pose a serious threat to human health. They have long been involved in a range of genetically inherited diseases, as well as cancer, age and neurodegenerative diseases such as Alzheimer’s.
It now emerges that mutagenic threats to cell viability could be far more widespread than previously understood. In a new study, Michael Lynch and his colleagues point out that DNA mutation itself may represent only a fraction of the health-related damage caused by mutagens.
The study highlights the potential of mutagenic fertilizers to influence transcription process, when DNA sequence is converted (or transcribed) to mRNA, an intermediate stage before protein translation.
The findings of the research, (which highlights mutagenic transcription errors in yeast, worms, flies, and mice), indicate that the harmful effects of mutagens on transcription tend to be much more widespread than before. previously understood – a fact that can have a profound effect on human health.
Our results have the potential to transform the way we think about the outcome of environmental mutagens. “
Professor Michael Lynch, Director of the Biodesign Center for Machines in Evolution and researcher, ASU School of Life Sciences
The results of the research appear in the current issue of the journal PNAS.
Endangered cells
Because of their important role in disease processes, mutagenic fertilizers have long been the subject of scientific study. Such agents include sunlight and other sources of radiation, chemotherapeutics, toxic byproducts of cell metabolism, or chemicals present in food and water.
Mutagens can damage the DNA, which can later form a snowball when cells divide, and DNA reproduction multiplies these errors. Such mutations, if not corrected through DNA testing devices, can be passed on to subsequent generations and depending on where they appear on the three billion letter code of human DNA, could it adversely affects health, in some cases, with fatal consequences.
But even if it is repaired before reproduction, DNA damaged by translocation can also inhibit transcription – the process of RNA production from DNA sequences. This can occur when RNA reads a polymerase, an enzyme that travels on a single strand of DNA, secreting component RNA strands, a layer of inverted DNA, causing an error in the resulting RNA transcription.
Because RNA transcripts are the templates for protein extraction, aberrant protein transcription errors can be harmful to health or completely eliminate protein synthesis. It is already known that, even under the best conditions, transcription error rates of orders of magnitude are higher than those of DNA level.
RNA: a series of errors?
Although transcription errors have long been recognized, their measurement has been challenging. The new study outlines an innovative mechanism for detecting transcription errors caused by mutagens and separating them from experimental objects – mutations caused when a library edits RNA transcripts through replication processes. -writing and series.
The method described involves the use of parallel sequencing technology to directly identify those errors in RNA sequence that are directly caused by mutagen activity. The results show that at least some mutagenic compounds are strong sources of both genomic mutations and abundant transcription errors.
The circular order assay described in the study creates transcripts in the rewritten message, providing a way to read the resulting serial DNA. In this way, researchers can confirm that the transcript errors observed are due to mutagen effects on transcription and not an artifact of sample preparation.
The DNA molecule has been shown to be particularly vulnerable to a type of mutagens called alkylating agents. One of these, called MNNG, was used to make transcription errors on the four study organisms. The effects studied were dose-dependent, with higher levels of mutagen causing a similar increase in transcription errors.
Hidden mistakes can be costly to your health
Transcriptional errors differ from mutations in the genome in at least one critical respect. While DNA reproduction during cell division works to increase mutations to the genome, transcription errors can accumulate in non-dividing cells, with a single mutated DNA template causing multiple RNA transcripts or -normal.
The full impact of these transcription errors on human health remains largely approximate as they have not been able to be studied to date. Using the new method, researchers can mine the transcript – the library full of live cell RNA transcripts, detecting errors caused by mutagens.
While the new research offers hope for a deeper understanding of the connection between different mutagens and human health, it is also a cautionary tale. Predisposition to mutational deficiencies in DNA sequencing may have blinded science to the potential effects of agents leading to transcription errors without leaving permanent traces in the genome.
This fact raises the possibility that a wide range of environmental factors as well as chemicals and foods that are considered safe for human consumption are required, depending on their ability to perform mutagenesis transcription. Further, transcription errors in both dividing and non-dividing cell types are the major players in the complex processes of physical age and mental decline.