Nav: Home

DNA research offers clues on cell mutation

January 06, 2016

A team of researchers from Colorado State University has been studying DNA damage in living cells to learn more about how genetic abnormalities arise. It has long been known that DNA molecules in every cell get constantly damaged by things from the outside environment, like sunlight, cigarette smoke and radiation. However, more recently researchers have discovered that sources from within the cell itself can sometimes be even more damaging.

DNA, or deoxyribonucleic acid, is found in the nucleus of every cell. It is the code for the traits we have as human beings, and it serves as the warehouse of information needed to make a cell work. When something goes wrong with DNA, it can lead to a mutation and changes in the cell, and can sometimes lead to disease.

In a study highlighted in a recent issue of Genetics, the team -- led by J. Lucas Argueso, CSU assistant professor and Boettcher Investigator in the Department of Environmental & Radiological Health Sciences -- found that RNA, or ribonucleic acid, has a new and important part in this process. CSU researchers worked in close in collaboration with scientists from the National Institute of Environmental Health Sciences in North Carolina.

RNA is a molecule that plays a central role in the function of genes. It is the "business" end of a genome. The building blocks that cells use for making RNA are knows as ribonucleotides, which was the focus of the research paper.

"You don't hear as much about RNA, but cells actually have much more RNA than DNA," Argueso said.

Cells also have more ribonucleotides than deoxyribonucleotides, the building blocks for making DNA. Since the two are chemically very similar, it is quite common for cells to mistakenly incorporate RNA pieces into DNA.

Argueso and his team -- including Hailey Conover, Ph.D. student in Cell & Molecular Biology and lead author of the study, and Deborah Afonso Cornelio, a post-doctoral researcher -- are looking at what happens to yeast cells when they are unable to accurately remove RNA from DNA.

"The same problem happens in humans, carrots, butterflies, and yeast cells, the model organism used in our lab," Argueso said. "The same yeast that is used to bake bread and to brew beer is an incredibly useful biomedical research model."

Findings from this study have direct implications for children with Aicardi-Goutieres syndrome, a devastating disorder that affects the brain, the immune system and the skin.

"This is a very serious disease that affects children born without a critical enzyme that removes the RNA building blocks from DNA," Argueso said. "Our model yeast cells have been engineered to have the same basic genetic defect as Aicardi-Goutieres children so that we can investigate this problem at its very core."

What's next for the team? Argueso said they want to extend their work to cancer research. The team wants to determine how ribonucleotides increase chromosome abnormalities and whether those increases are asymmetric, depending on which of the two strands of DNA the ribonucleotides are introduced.

Most cancers have some form of alteration in chromosomal structure, though Argueso said that breast and ovarian cancers are by far the most affected by this issue.

In addition, with some forms of chemotherapy that have been used for a long time, the mechanism of action is to decrease the production of DNA building blocks.

"Cancer cells reproduce quickly," Argueso said. "To do that, the cells need DNA building blocks. Chemotherapy is used to decrease the building blocks. However, when you reduce the number of DNA building blocks, you push the cancer cells into a corner, where they end up putting in more RNA building blocks into the DNA."

In other words, the very thing that the chemotherapy agent is encouraging cancer cells to incorporate causes them to acquire even more mutations. This could help explain why cancers often recur in more aggressive forms after someone goes into remission.

"This unintended consequence could be one of the mechanisms making that happen," Argueso said.
-end-


Colorado State University

Related Chemotherapy Articles:

Less chemotherapy may have more benefit in rectal cancer
GI Cancers Symposium: Colorado study of 48 patients with locally advanced rectal cancer receiving neoadjuvant chemotherapy, found that patients receiving lower-than-recommended doses in fact saw their tumors shrink more than patients receiving the full dose.
Male fertility after chemotherapy: New questions raised
Professor Delbès, who specializes in reproductive toxicology, conducted a pilot study in collaboration with oncologists and fertility specialists from the McGill University Health Centre (MUHC) on a cohort of 13 patients, all survivors of pediatric leukemia and lymphoma.
'Combo' nanoplatforms for chemotherapy
In a paper to be published in the forthcoming issue in NANO, researchers from Harbin Institute of Technology, China have systematically discussed the recent progresses, current challenges and future perspectives of smart graphene-based nanoplatforms for synergistic tumor therapy and bio-imaging.
Nanotechnology improves chemotherapy delivery
Michigan State University scientists have invented a new way to monitor chemotherapy concentrations, which is more effective in keeping patients' treatments within the crucial therapeutic window.
Novel anti-cancer nanomedicine for efficient chemotherapy
Researchers have developed a new anti-cancer nanomedicine for targeted cancer chemotherapy.
Ending needless chemotherapy for breast cancer
A diagnostic test developed at The University of Queensland might soon determine if a breast cancer patient requires chemotherapy or would receive no benefit from this gruelling treatment.
A homing beacon for chemotherapy drugs
Killing tumor cells while sparing their normal counterparts is a central challenge of cancer chemotherapy.
Chemotherapy or not?
Case Western Reserve University researchers and partners, including a collaborator at Cleveland Clinic, are pushing the boundaries of how 'smart' diagnostic-imaging machines identify cancers -- and uncovering clues outside the tumor to tell whether a patient will respond well to chemotherapy.
Researchers use radiomics to predict who will benefit from chemotherapy
Using data from computed tomography (CT) images, researchers may be able to predict which lung cancer patients will respond to chemotherapy, according to a new study.
How drugs can minimize the side effects of chemotherapy
Researchers at the University of Zurich have determined the three-dimensional structure of the receptor that causes nausea and vomiting as a result of cancer chemotherapy.
More Chemotherapy News and Chemotherapy Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.