PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

An enzyme that fixes broken DNA sometimes destroys it instead, Stanford researchers find

2014-11-26
(Press-News.org) Enzymes inside cells that normally repair damaged DNA sometimes wreck it instead, researchers at the Stanford University School of Medicine have found. The insight could lead to a better understanding of the causes of some types of cancer and neurodegenerative disease.

In a paper to be published online Nov. 27 in Molecular Cell, the researchers explain how the recently discovered mechanism of DNA damage occurs when genetic transcripts, composed of RNA, stick to the DNA instead of detaching from it.

Certain enzymes, called endonucleases, are attracted to DNA/RNA hybrids that form when gene transcription goes awry -- and they cut the DNA like scissors to damage it.

The researchers conducted the study with human cells in culture, using molecular biology techniques to turn off specific genes. This allowed them to induce cells to form the hybrids and to see what would happen when various enzymes were inhibited.

"What we found is when we get rid of these endonucleases, we don't see the damage," said Karlene Cimprich, PhD, professor of chemical and systems biology and the paper's senior author. "When those nucleases are present, they cut the DNA in the hybrid."

Both helpful and harmful

What's really interesting, said Cimprich, is these same enzymes are noted for fixing DNA damage. "They take part in the repair of DNA lesions from sunlight and certain chemicals, like those found in cigarette smoke," she said. The structures formed by the hybrid of RNA and DNA are similar to those formed in cells damaged by ultraviolet light.

"What we believe happens is that the repair machinery misrecognizes these structures and cuts them," she said. She and her colleagues have launched more experiments to figure out why this happens.

The study not only opens up new avenues for understanding DNA damage, it expands the role of the messenger RNA molecule. In the last decade, researchers have discovered many new roles for RNA, aside from its long-recognized role in providing instructions for building proteins.

"The messenger RNA is known to transmit the information and make the proteins," said Cimprich. "But we found that if it isn't removed properly it destroys the DNA that originally encoded it."

A study published by Cimprich and colleagues in Molecular Cell in 2009 alerted researchers to the importance of RNA in DNA damage. Their genomewide screen to identify factors that help fix DNA damage found hundreds of different molecules, some of which the researchers expected. But most of the molecules were surprises. And most interacted in some way with RNA, which pointed to RNA as a culprit in causing DNA damage.

"When we thought about what would cause DNA damage in cells, we thought about problems with DNA replication and DNA repair," she said. "But now we're beginning to see that problems with RNA can also feed back to the DNA."

Understanding role of enzymes

Now the researchers are trying to understand why some of the enzymes that control transcription are causing DNA damage, with an eye to understanding the roots of some cancers. "A lot of oncogenes are transcription factors. We're looking at whether those cause genome instability by making hybrids like those we've seen. Is this a different route to DNA damage and cancer?" Cimprich said.

"Recent work has also implicated these hybrids in neurodegenerative diseases, including Fragile X syndrome, Friedreich's ataxia and amyotrophic lateral sclerosis type 4," said Julie Sollier, PhD, the lead author of the paper and a postdoctoral researcher. "We would like to explore the potential role of the endonucleases we identified in these diseases as well."

INFORMATION:

Other Stanford co-authors are graduate student Caroline Townsend Stork and former graduate student Renee Paulsen, PhD. Researchers at the University of Seville in Spain also contributed to the paper.

The research was supported by the Spanish Ministry of Economy and Competitiveness, the European Union and the National Institutes of Health (grant GM100489).

Information about Stanford's Department of Chemical and Systems Biology, which also supported this work, is available at http://chemsysbio.stanford.edu/.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://med.stanford.edu/school.html. The medical school is part of Stanford Medicine, which includes Stanford Health Care and Lucile Packard Children's Hospital Stanford. For information about all three, please visit http://med.stanford.edu.

Print media contact: Rosanne Spector at (650) 725-5374 (manishma@stanford.edu) Broadcast media contact: Margarita Gallardo at (650) 723-7897 (mjgallardo@stanford.edu)



ELSE PRESS RELEASES FROM THIS DATE:

iPS cells used to correct genetic mutations that cause muscular dystrophy

iPS cells used to correct genetic mutations that cause muscular dystrophy
2014-11-26
Researchers at the Center for iPS Cell Research and Application (CiRA), Kyoto University, show that induced pluripotent stem (iPS) cells can be used to correct genetic mutations that cause Duchenne muscular dystrophy (DMD). The research, published in Stem Cell Reports, demonstrates how engineered nucleases, such as TALEN and CRISPR, can be used to edit the genome of iPS cells generated from the skin cells of a DMD patient. The cells were then differentiated into skeletal muscles, in which the mutation responsible for DMD had disappeared. DMD is a severe muscular degenerative ...

Enzyme may be key to cancer progression in many tumors

Enzyme may be key to cancer progression in many tumors
2014-11-26
Mutations in the KRAS gene have long been known to cause cancer, and about one third of solid tumors have KRAS mutations or mutations in the KRAS pathway. KRAS promotes cancer formation not only by driving cell growth and division, but also by turning off protective tumor suppressor genes, which normally limit uncontrolled cell growth and cause damaged cells to self-destruct. A new University of Iowa study provided a deeper understanding of how KRAS turns off tumor suppressor genes and identifies a key enzyme in the process. The findings, published online Nov. 26 in the ...

Research on a rare cancer exposes possible route to new treatments

2014-11-26
SALT LAKE CITY--Researchers from Huntsman Cancer Institute (HCI) at the University of Utah (U of U) discovered the unusual role of lactate in the metabolism of alveolar soft part sarcoma (ASPS), a rare, aggressive cancer that primarily affects adolescents and young adults. The study also confirmed that a fusion gene is the cancer-causing agent in this disease. The research results were published online in the journal Cancer Cell Nov. 26, 2014. ASPS tumor cells contain a chromosomal translocation--strands of DNA from two chromosomes trade places. The two strands fuse ...

University of Minnesota engineers make sound loud enough to bend light on a computer chip

University of Minnesota engineers make sound loud enough to bend light on a computer chip
2014-11-26
MINNEAPOLIS / ST. PAUL (11/26/2014)--During a thunderstorm, we all know that it is common to hear thunder after we see the lightning. That's because sound travels much slower (768 miles per hour) than light (670,000,000 miles per hour). Now, University of Minnesota engineering researchers have developed a chip on which both sound wave and light wave are generated and confined together so that the sound can very efficiently control the light. The novel device platform could improve wireless communications systems using optical fibers and ultimately be used for computation ...

Copper on the brain at rest

Copper on the brain at rest
2014-11-26
In recent years it has been established that copper plays an essential role in the health of the human brain. Improper copper oxidation has been linked to several neurological disorders including Alzheimer's, Parkinson's, Menkes' and Wilson's. Copper has also been identified as a critical ingredient in the enzymes that activate the brain's neurotransmitters in response to stimuli. Now a new study by researchers with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) has shown that proper copper levels are also essential to the health ...

UNL study details laser pulse effects on electron behavior

UNL study details laser pulse effects on electron behavior
2014-11-26
Lincoln, Neb., Nov. 26, 2014 -- By solving a six-dimensional equation that had previously stymied researchers, University of Nebraska-Lincoln physicists have pinpointed the characteristics of a laser pulse that yields electron behavior they can predict and essentially control. It's long been known that laser pulses of sufficient intensity can produce enough energy to eject electrons from their ultrafast orbits around an atom, causing ionization. An international team led by the UNL researchers has demonstrated that the angles at which two electrons launch from a helium ...

Tropical depression 21W forms, Philippines under warnings

Tropical depression 21W forms, Philippines under warnings
2014-11-26
The Tropical Rainfall Measuring Mission or TRMM satellite provided rainfall data as Tropical Depression 21W was making landfall in the southern Philippines on Nov. 26. TRMM revealed areas of heavy rainfall in fragmented bands east of the center of circulation, where rain was falling at more than 1 inch (25 mm) per hour. TRMM rainfall data was overlaid on infrared data from the Japan Meteorological Agency's MTSAT-1 satellite that showed Tropical Depression 21W's (TD21W) clouds extended from western Mindanao, east into the Philippine Sea. On Nov. 26, there were a number ...

SLU researcher finds an off switch for pain

2014-11-26
ST. LOUIS-- In research published in the medical journal Brain, Saint Louis University researcher Daniela Salvemini, Ph.D. and colleagues within SLU, the National Institutes of Health (NIH) and other academic institutions have discovered a way to block a pain pathway in animal models of chronic neuropathic pain including pain caused by chemotherapeutic agents and bone cancer pain suggesting a promising new approach to pain relief. The scientific efforts led by Salvemini, who is professor of pharmacological and physiological sciences at SLU, demonstrated that turning on ...

Minimally invasive disc surgery is a pain in the neck

2014-11-26
Hamilton, ON (Nov. 26, 2014) - McMaster University researchers have found that current evidence does not support the routine use of minimally invasive surgery to remove herniated disc material pressing on the nerve root or spinal cord in the neck or lower back. In comparing it with open surgery, they found that while minimally invasive surgery for cervical or lumbar discectomy may speed up recovery and reduce post-operative pain, it does not improve long-term function or reduce long-term extremity pain. Minimally invasive surgery for discectomy also requires advanced ...

Brain researchers pinpoint gateway to human memory

2014-11-26
This news release is available in German. The human brain continuously collects information. However, we have only basic knowledge of how new experiences are converted into lasting memories. Now, an international team led by researchers of the University of Magdeburg and the German Center for Neurodegenerative Diseases (DZNE) has successfully determined the location, where memories are generated with a level of precision never achieved before. The team was able to pinpoint this location down to specific circuits of the human brain. To this end the scientists used a ...

LAST 30 PRESS RELEASES:

‘Molecular shield’ placed in the nose may soon treat common hay fever trigger

Beetles under climate stress lay larger male eggs: Wolbachia infection drives adaptive reproduction strategy in response to rising temperature and CO₂

Groundbreaking quantum study puts wave-particle duality to work

Weekly injection could be life changing for Parkinson’s patients

Toxic metals linked to impaired growth in infants in Guatemala

Being consistently physically active in adulthood linked to 30–40% lower risk of death

Nerve pain drug gabapentin linked to increased dementia, cognitive impairment risks

Children’s social care involvement common to nearly third of UK mums who died during perinatal period

‘Support, not judgement’: Study explores links between children’s social care involvement and maternal deaths

Ethnic minority and poorer children more likely to die in intensive care

Major progress in fertility preservation after treatment for cancer of the lymphatic system

Fewer complications after additional ultrasound in pregnant women who feel less fetal movement

Environmental impact of common pesticides seriously underestimated

The Milky Way could be teeming with more satellite galaxies than previously thought

New study reveals surprising reproductive secrets of a cricket-hunting parasitoid fly

Media Tip Sheet: Symposia at ESA2025

NSF CAREER Award will power UVA engineer’s research to improve drug purification

Tiny parasitoid flies show how early-life competition shapes adult success

New coating for glass promises energy-saving windows

Green spaces boost children’s cognitive skills and strengthen family well-being

Ancient trees dying faster than expected in Eastern Oregon

Study findings help hone precision of proven CVD risk tool

Most patients with advanced melanoma who received pre-surgical immunotherapy remain alive and disease free four years later

Introducing BioEmu: A generative AI Model that enables high-speed and accurate prediction of protein structural ensembles

Replacing mutated microglia with healthy microglia halts progression of genetic neurological disease in mice and humans

New research shows how tropical plants manage rival insect tenants by giving them separate ‘flats’

Condo-style living helps keep the peace inside these ant plants

Climate change action could dramatically limit rising UK heatwave deaths

Annual heat-related deaths projected to increase significantly due to climate and population change

Researchers discover new way cells protect themselves from damage

[Press-News.org] An enzyme that fixes broken DNA sometimes destroys it instead, Stanford researchers find