Women Beware: Sugary Beverages may Increase Risk of Endometrial Cancer

Here is a new risk for cancer of the uterus for women that come from too many sugary drinks.

Intense fears of being hit with gynecological cancers leads women to search aggressively for manners in which to prevent cancer. Information dealing with how women many be able to prevent cancer is always welcomed. News that nutrition can effect the risks for cancer has generated a great deal of interest in eating better. A recent report that sugary beverages may increase the risk for endometrial cancer is therefore of great significance.

Higher intake of sugar sweetened soft drinks is associated with an increased risk of type I, but not type II, endometrial cancer, according to a research report in the journal Cancer, Epidemiology, Biomarkers and Prevention. Prior to this research sugar-sweetened beverage intake was found to be associated with an increased risk of obesity and type II diabetes. However, any association between consumption of sugary beverages and endometrial cancer was not clear.

Endometrial cancer is the most common tumor which is found in the female reproductive system, writes Memorial Sloan Kettering Cancer Center. It has been estimated by the American Cancer Society that greater than 40,100 women are diagnosed with this cancer every year in the United States. During a lifetime approximately one in 41 women will develop endometrial cancer.

Prior to menopause the ovaries of women generally produce two primary types of hormones: estrogen and progesterone. Endometrial cell growth is promoted by estrogen. Endometrial cell growth is inhibited by progesterone. Endometrial cancer has been observed to occur more often in women who have high circulating levels of estrogen and low levels of progesterone. Factors which are associated with increased exposure to estrogen over time may lead to an increased risk of endometrial cancer.

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The primary risk factors for endometrial cancer are:

1: Obesity, particularly being greater than 50 pounds overweight

2: Early menstruation, periods starting before age 12

3: Late menopause, after age 52

4: Never having given birth or a history of infertility

5: Ovarian diseases, such as polycystic ovaries

6: Tamoxifen use

Further considerations about risk factors for endometrial cancer are shared in an article by EmaxhHealth reporter Deborah Mitchell.

Women suffering from endometrial cancer generally complain of postmenopausal bleeding or irregular vaginal bleeding. About 33 percent of women who experience vaginal bleeding after menopause are found to have endometrial cancer. A large percent of endometrial cancers are found in very early stages because of abnormal uterine bleeding. The discharge which s associated with endometrial cancer is often pink, watery, or white instead of red. Clearly, any abnormal vaginal bleeding should be immediately checked out by a physician.

Other symptoms which are often associated with endometrial cancer include:

1: Difficult or painful urination or pain during intercourse.

2: Pelvic pain and experience

3: Unexplained weight loss

Options for treating endometrial cancer include surgery, radiation therapy, hormone therapy, and chemotherapy. Natural interventions, such as exercise, good nutrition, and adequate rest and sleep certainly may help improve the prognosis of endometrial cancer.

In a review of this study by researchers at the University of Minnesota School of Public Health, MedPage Today writes that the most common type of endometrial cancer was observed about 80 percent more often in postmenopausal women who regularly drank sugar-sweetened drinks in comparison with women who did not consume these drinks.

Furthermore, the prevalence of estrogen-dependent endometrial cancer was seen to increase in a steady manner and and significantly with increased weekly consumption of sugar-sweetened drinks. The hazard was increased by 78 percent among women who consumed four or more servings a week. The same association was not found with the less common no hormonal endometrial cancer.

The researchers stated, "We found that higher consumption of sugar-sweetened beverages was associated with higher risk of estrogen-dependent type I endometrial cancer, regardless of body mass index, physical activity, a history of diabetes, and cigarette smoking." Higher risk of type I endometrial cancer was found in association with higher consumption of sugars. The risk of estrogen-independent type II endometrial cancer was not found to be associated with consumption levels of sugar sweetened beverages and sugars.

A possible explanation for these findings has been the rise on prevalence of obesity found with the rise in consumption of sugar-containing drink in the U. S. This may explain the association of sugary drinks with endometrial cancer, which occurs disproportionately more often in obese women.

Obesity has been found to be associated with about 50 percent of type I endometrial cancers in developed nations. An association has been found in epidemiologic studies between higher consumption of sugar-sweetened drinks and higher risk of obesity and type 2 diabetes. This all highlights the likelihood of a biologic explanation for sugar-sweetened drink consumption being a contributing factor in the development of endometrial cancer.

In this study factors which were found to be associated with endometrial cancer were:

1: Older age

2: Higher BMI

3: Higher waist-hip ratio

4: History of diabetes

5: Early menarche

6: Delayed menopause

7: Any estrogen therapy

A dose-dependent association between increasing consumption of sugar-sweetened drinks, excluding fruit juices, and development of type I endometrial cancer, was found. Women who had the highest consumption of sugared beverages had a 72 percent increased risk of developing type I endometrial cancer in comparison with women with the lowest consumption of sugary drinks. There was no association found between consumption of sugar-free drinks and endometrial cancer risk.

There was also no association found with consumption of sweets and baked goods. There was a trend seen towards increased risk of endometrial cancer with increasing consumption of sucrose and glucose. The finding of an association between drinking sugar-sweetened drinks and the development of endometrial cancer was not surprising due to the cancer's association with obesity.

However, the lack of association found between sugary foods and endometrial cancer was puzzling, and warrants further investigation.

An interesting consideration for lowering the risk of endometrial cancer is raised by EmaxHealth reporter Robin Wulffson, MD in an article which reviews an association between reducing uterine cancer risk and drinking coffee.

It has been my experience that women generally live in great fear of being hit with gynecological cancers. There is often a sense of panic and urgency experienced with any episodes of irregular menstrual bleeding, which certainly warrants immediate medical attention. Findings that increased consumption of sugary drinks and obesity are associated with an increased risk for endometrial cancer should be shared with patients. It is my professional opinion that counseling women about these facts may have a dramatic impact on the prevalence of endometrial cancer and on outcomes in patients afflicted with this illness.

By Harold Mandel

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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Clues of Antibiotic Use, Resistance in US Children's Hospitals

Nov. 23, 2013 — Two studies published in the December issue of Infection Control and Hospital Epidemiology show antibiotic resistance patterns for children have held stable over a seven-year period and surgical patients in U.S. children's hospitals account for 43 percent of all antibiotic use in children's hospitals, presenting an opportunity for targeted intervention.

The release of the findings coincides with the Centers for Disease Control and Prevention's (CDC) Get Smart about Antibiotics Week, an annual weeklong observance on antibiotic resistance and the importance of appropriate antibiotic use. The Society for Healthcare Epidemiology of America publishesInfection Control and Hospital Epidemiology and is a proud partner of Get Smart about Antibiotics Week.

"Inappropriate use of antibiotics can have serious and global consequences on the utility of these drugs and the spread of resistant bacteria," said Neil Fishman, MD, a past-president of SHEA and Associate Chief Medical Officer at the University of Pennsylvania Health System. "These studies help complement our collective knowledge of the resistant bacteria in vulnerable children populations and give us a better understanding of how children's hospitals use antibiotics."

Antibiotic Resistance Holds Stable in Children's Hospitals Because there are few data describing antibiotic resistance in pediatric healthcare institutions, researchers from Johns Hopkins University School of Medicine reviewed institutional patterns of antibiotic susceptibility from 55 institutions reflecting data from 2005-2011.

They found antibiotic resistance has remained relatively stable for the majority of tested organisms over the seven-year period. The results must be considered with caution in the context of the limited number of new antibiotic agents coming down the pipeline and the increasing prevalence of drug-resistant infections among adults.

"Unless we are judicious with our use of antibiotics in children, we may encounter a resistance scenario similar to what is occurring in the adult population," said Pranita Tamma, MD, lead author of the study. "Pooling these data allows us to identify nationwide patterns of antibiotic resistance in children's hospitals, allows cross-hospital benchmarking, and allows under-resourced hospitals to use this information to better inform empiric antibiotic treatment practices."

Antimicrobial Stewardship in Children's Hospitals Although mechanisms for implementing antimicrobial stewardship programs (ASPs) have been reported elsewhere, data-driven approaches to prioritize specific conditions and antibiotics for intervention have not been established. Researchers from The Children's Hospital of Philadelphia used a retrospective cross-sectional study to develop a strategy for identifying high-impact targets for stewardship efforts.

"The majority of patients admitted to U.S. children's hospitals receive antibiotic therapy," said Jeffrey Gerber, MD, lead author of the study. "Antimicrobial stewardship programs have been recommended to optimize antibiotic use and manage and reduce variability in care, helping reduce costs while maintaining or improving outcomes."

Analyzing more than 500,000 inpatient admissions and nearly three million patient-days from 32 hospitals, researchers found that surgical patients received 43 percent of all prescribed antibiotic therapy and a small number of clinical conditions contributed significantly to overall use, presenting an opportunity for ASPs to target these areas.

The four conditions associated with the highest use of antibiotics among pediatric patients were pneumonia, appendicitis, cystic fibrosis, and skin and soft-tissue infections. These conditions represented one percent of diagnoses, but accounted for more than 10 percent of antibiotic use.

Wide variability in antibiotic use occurred among three of the conditions: pneumonia, appendicitis, and cystic fibrosis. The researchers believe pediatric antimicrobial stewardship efforts should prioritize standardizing treatment approaches for these conditions.

Journal References:

1.     Pranita D. Tamma, Gwen L. Robinson, Jeffrey S. Gerber, Jason G. Newland, Chloe M. DeLisle, Theoklis E. Zaoutis, Aaron M. Milstone. Pediatric Antimicrobial Susceptibility Trends across the United States. Infection Control and Hospital Epidemiology, December 2013

2.     Jeffrey S. Gerber, Matthew P. Kronman, Rachel K. Ross, Adam L. Hersh, Jason G. Newland, Talene A. Metjian, Theoklis E. Zaoutis. Identifying Targets for Antimicrobial Stewardship in Children's Hospitals. Infection Control and Hospital Epidemiology, December 2013

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The above story is based on materials provided by Society for Healthcare Epidemiology of America.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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Archaeologists Discover Largest, Oldest Wine Cellar in Near East: 3,700 Year-Old Store Room Held 2,000 Liters of Strong, Sweet Wine

Nov. 23, 2013 — Would you drink wine flavored with mint, honey and a dash of psychotropic resins? Ancient Canaanites did more than 3,000 years ago.

Archaeologists have unearthed what may be the oldest -- and largest -- ancient wine cellar in the Near East, containing forty jars, each of which would have held fifty liters of strong, sweet wine. The cellar was discovered in the ruined palace of a sprawling Canaanite city in northern Israel, called Tel Kabri. The site dates to about 1,700 B.C. and isn't far from many of Israel's modern-day wineries.

"This is a hugely significant discovery -- it's a wine cellar that, to our knowledge, is largely unmatched in age and size," says Eric Cline chair of the Department of Classical and Near Eastern Languages and Civilizations of at The George Washington University. Cline and Assaf Yasur-Landau, chair of the Department of Maritime Civilizations at the University of Haifa, co-directed the excavation. Andrew Koh, assistant professor of classical studies at Brandeis University, was an associate director.

The team's findings will be presented this Friday in Baltimore at the annual meeting of the American Schools of Oriental Research.

Koh, an archaeological scientist, analyzed the jar fragments using organic residue analysis. He found molecular traces of tartaric and syringic acid, both key components in wine, as well as compounds suggesting ingredients popular in ancient wine-making, including honey, mint, cinnamon bark, juniper berries and resins. The recipe is similar to medicinal wines used in ancient Egypt for two thousand years.

Koh also analyzed the proportions of each diagnostic compound and discovered remarkable consistency between jars.

"This wasn't moonshine that someone was brewing in their basement, eyeballing the measurements," Koh notes. "This wine's recipe was strictly followed in each and every jar."

Important guests drank this wine, notes Yasur-Landau.

"The wine cellar was located near a hall where banquets took place, a place where the Kabri elite and possibly foreign guests consumed goat meat and wine," he says.

At the end of the season, the team discovered two doors leading out of the wine cellar -- one to the south, and one to the west. Both probably lead to additional storage rooms. They'll have to wait until 2015 to find out for sure.

Source:

The above story is reprinted from materials provided by University of Copenhagen.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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DNA Packaging Discovery Reveals Principles by Which CRC Mutations May Cause Cancer (Eagle Group- Nov19, 2012)

The discovery, by Bradley R. Cairns, PhD, Senior Director of Basic Science at HCI and a professor in the Department of Oncological Sciences, is reported in this week's online issue of the journal Nature.

Cairns's research focuses on chromatin remodeling complexes (CRCs), which are cellular protein complexes that behave like motors, expanding or compacting different portions of DNA to either express or silence genes, respectively. Before, scientists thought that the motor within CRCs waits at rest until it receives instructions. Cairns and co-author Cedric R. Clapier show that the motor within a key CRC responsible for gene packaging and assembly is intrinsically turned on, and instead requires specific instructions to turn it off.

"Many articles in the research literature show that CRCs are mutated in cancer cells. They are intimately involved in regulating gene expression -- responsible for correctly packaging genes that control growth proliferation and for unpackaging tumor suppressors," said Cairns. "This research reveals principles by which CRC mutations could cause cancer."

Chromosomes are made of long DNA strands compressed around nodes of protein called nucleosomes; when DNA is compressed, the genes in that area are turned off. Some CRCs, called disassembly CRCs, act as motors that unwind sections of DNA chains, making genes active for a given cell process. Another type, called assembly CRCs, rewinds the DNA chain, recompressing it when the process is complete. The unwind-rewind cycle is repeated continuously throughout a cell's life.

In this study, Cairns and Clapier focused on assembly CRCs. "Before this research, we thought that the motor was off unless a protein coming from another part of the cell turned it on," said Cairns. "Researchers have been searching for the switch by looking at the CRC motor to see what binds to it.

"As it turns out, we discovered that the CRC motor already carries on its flank a 'switch' that inhibits its action until a marker sequence, located on the nucleosome, is encountered. The marker flips the inhibitor switch and allows the CRC to crank the DNA chain back around the nucleosome, promoting gene packaging and silencing" Cairns said. "Our results change where future researchers should be looking to understand how CRCs are regulated -- not at the CRC motor itself, but at the 'switches' that flank the motor."

The study also describes a measuring function on the CRC that checks for the correct distance between one nucleosome and the next, telling the motor to switch off at the proper time, a function needed for gene silencing.

Cairns's lab will now examine this same switching concept in disassembly remodelers. "There are additional remodeler families with alternative functions, like DNA repair," said Cairns. "We think this concept will apply to them as well."

This research was supported by funding from the National Institutes of Health (GM60415 and CA042014) and from the Howard Hughes Medical Institute.

Journal Reference:

1.      Cedric R. Clapier, Bradley R. Cairns. Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes. Nature, 2012; DOI:10.1038/nature11625

Source:

The above story is reprinted from materials provided by University of Utah Health Sciences.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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Reconsidering Cancer's Bad Guy (Eagle Group- Nov 19, 2012)

Researchers at the University of Copenhagen have found that a protein, known for causing cancer cells to spread around the body, is also one of the molecules that trigger repair processes in the brain.

How to repair brain injuries is a fundamental question facing brain researchers. Scientists have been familiar with the protein S100A4 for some time as a factor in metastasis, or how cancer spreads. However it's the first time the protein has been shown to play a role in brain protection and repair.

"This protein is not normally in the brain, only when there's trauma or degeneration. When we deleted the protein in mice we discovered that their brains were less protected and able to resist injury. We also discovered that S100A4 works by activating signalling pathways inside neurons," says Postdoc Oksana Dmytriyeva, who worked on the research in a team at the Protein Laboratory in the Department of Neuroscience and Pharmacology at the University of Copenhagen.

The villain turns out to be the hero

This research stands on the shoulders of many years of work on S100A4 in its deadlier role in cancer progression. The discovery represents a significant development for the new Neuro-Oncology Group that moved to the University of Copenhagen's Protein Laboratory Group from the Danish Cancer Society in October.

"We were surprised to find this protein in this role, as we thought it was purely a cancer protein. We are very excited about it and we're looking forward to continuing our research in a practical direction. We hope that the findings will eventually benefit people who need treatment for neurodegenerative disorders like Alzheimer's disease, although obviously we have a long way to go before we get to that point," says Oksana Dmytriyeva.

The scientific paper The metastasis-promoting S100A4 protein confers neuroprotection in brain injury can be found online in the journal Nature Communications.

Journal Reference:

1.      Oksana Dmytriyeva, Stanislava Pankratova, Sylwia Owczarek, Katrin Sonn, Vladislav Soroka, Christina M. Ridley, Alexander Marsolais, Marcos Lopez-Hoyos, Noona Ambartsumian, Eugene Lukanidin, Elisabeth Bock, Vladimir Berezin, Darya Kiryushko. The metastasis-promoting S100A4 protein confers neuroprotection in brain injury.Nature Communications, 2012; 3: 1197 DOI:10.1038/ncomms2202

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The above story is reprinted from materials provided by University of Copenhagen.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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Breakthrough Nanoparticle Halts Multiple Sclerosis in Mice, Offers Hope for Other Immune-Related Diseases (Eagle Group-Nov 19, 2012)

The new nanotechnology also can be applied to a variety of immune-mediated diseases including Type 1 diabetes, food allergies and airway allergies such as asthma.

In MS, the immune system attacks the myelin membrane that insulates nerves cells in the brain, spinal cord and optic nerve. When the insulation is destroyed, electrical signals can't be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness. About 80 percent of MS patients are diagnosed with the relapsing remitting form of the disease.

The Northwestern nanotechnology does not suppress the entire immune system as do current therapies for MS, which make patients more susceptible to everyday infections and higher rates of cancer. Rather, when the nanoparticles are attached to myelin antigens and injected into the mice, the immune system is reset to normal. The immune system stops recognizing myelin as an alien invader and halts its attack on it.

"This is a highly significant breakthrough in translational immunotherapy," said Stephen Miller, a corresponding author of the study and the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. "The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that's delivered."

"The holy grail is to develop a therapy that is specific to the pathological immune response, in this case the body attacking myelin," Miller added. "Our approach resets the immune system so it no longer attacks myelin but leaves the function of the normal immune system intact."

The nanoparticle, made from an easily produced and already FDA-approved substance, was developed by Lonnie Shea, professor of chemical and biological engineering at Northwestern's McCormick School of Engineering and Applied Science.

"This is a major breakthrough in nanotechnology, showing you can use it to regulate the immune system," said Shea, also a corresponding author. The paper will be published Nov. 18 in the journal Nature Biotechnology.

Miller and Shea are also members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. In addition, Shea is a member of the Institute for BioNanotechnology in Medicine and the Chemistry of Life Processes Institute.

Clinical Trial for Ms Tests Same Approach -- With Key Difference

The study's method is the same approach now being tested in multiple sclerosis patients in a phase I/II clinical trial -- with one key difference. The trial uses a patient's own white blood cells -- a costly and labor intensive procedure -- to deliver the antigen. The purpose of the new study was to see if nanoparticles could be as effective as the white blood cells as delivery vehicles. They were.

The Big Nanoparticle Advantage for Immunotherapy

Nanoparticles have many advantages; they can be readily produced in a laboratory and standardized for manufacturing. They would make the potential therapy cheaper and more accessible to a general population. In addition, these nanoparticles are made of a polymer called Poly(lactide-co-glycolide) (PLG), which consists of lactic acid and glycolic acid, both natural metabolites in the human body. PLG is most commonly used for biodegradable sutures.

The fact that PLG is already FDA approved for other applications should facilitate translating the research to patients, Shea noted. Miller and Shea tested nanoparticles of various sizes and discovered that 500 nanometers was most effective at modulating the immune response.

"We administered these particles to animals who have a disease very similar to relapsing remitting multiple sclerosis and stopped it in its tracks," Miller said. "We prevented any future relapses for up to 100 days, which is the equivalent of several years in the life of an MS patient."

Shea and Miller also are currently testing the nanoparticles to treat Type one diabetes and airway diseases such as asthma.

Nanoparticles Fool Immune System

In the study, researchers attached myelin antigens to the nanoparticles and injected them intravenously into the mice. The particles entered the spleen, which filters the blood and helps the body dispose of aging and dying blood cells. There, the particles were engulfed by macrophages, a type of immune cell, which then displayed the antigens on their cell surface. The immune system viewed the nanoparticles as ordinary dying blood cells and nothing to be concerned about. This created immune tolerance to the antigen by directly inhibiting the activity of myelin responsive T cells and by increasing the numbers of regulatory T cells which further calmed the autoimmune response.

"The key here is that this antigen/particle-based approach to induction of tolerance is selective and targeted. Unlike generalized immunosuppression, which is the current therapy used for autoimmune diseases, this new process does not shut down the whole immune system," said Christine Kelley, National Institute of Biomedical Imaging and Bioengineering director of the division of Discovery Science and Technology at the National Institutes of Health, which supported the research. "This collaborative effort between expertise in immunology and bioengineering is a terrific example of the tremendous advances that can be made with scientifically convergent approaches to biomedical problems."

"We are proud to share our expertise in therapeutics development with Dr. Stephen Miller's stellar team of academic scientists," said Scott Johnson, CEO, president and founder of the Myelin Repair Foundation. "The idea to couple antigens to nanoparticles was conceived in discussions between Dr. Miller's laboratory, the Myelin Repair Foundation's drug discovery advisory board and Dr. Michael Pleiss, a member of the Myelin Repair Foundation's internal research team, and we combined our efforts to focus on patient-oriented, clinically relevant research with broad implications for all autoimmune diseases. Our unique research model is designed to foster and extract the innovation from the academic science that we fund and transition these technologies to commercialization. The overarching goal is to ensure this important therapeutic pathway has its best chance to reach patients, with MS and all autoimmune diseases."

Journal Reference:

1.      Daniel R Getts, Aaron J Martin, Derrick P McCarthy, Rachael L Terry, Zoe N Hunter, Woon Teck Yap, Meghann Teague Getts, Michael Pleiss, Xunrong Luo, Nicholas JC King, Lonnie D Shea, Stephen D Miller. Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis. Nature Biotechnology, 2012; DOI:10.1038/nbt.2434

Source:

The above story is reprinted from materials provided by Northwestern University, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

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DNA Packaging Discovery Reveals Principles by Which CRC Mutations May Cause Cancer (Eagle Group- Nov 18, 2012)

Fundamental understanding about how DNA works will produce a "180-degree change in focus" for researchers who study how gene packaging regulates gene activity, including genes that cause cancer and other diseases.

The discovery, by Bradley R. Cairns, PhD, Senior Director of Basic Science at HCI and a professor in the Department of Oncological Sciences, is reported in this week's online issue of the journal Nature.

Cairns's research focuses on chromatin remodeling complexes (CRCs), which are cellular protein complexes that behave like motors, expanding or compacting different portions of DNA to either express or silence genes, respectively. Before, scientists thought that the motor within CRCs waits at rest until it receives instructions. Cairns and co-author Cedric R. Clapier show that the motor within a key CRC responsible for gene packaging and assembly is intrinsically turned on, and instead requires specific instructions to turn it off.

"Many articles in the research literature show that CRCs are mutated in cancer cells. They are intimately involved in regulating gene expression -- responsible for correctly packaging genes that control growth proliferation and for unpackaging tumor suppressors," said Cairns. "This research reveals principles by which CRC mutations could cause cancer."

Chromosomes are made of long DNA strands compressed around nodes of protein called nucleosomes; when DNA is compressed, the genes in that area are turned off. Some CRCs, called disassembly CRCs, act as motors that unwind sections of DNA chains, making genes active for a given cell process. Another type, called assembly CRCs, rewinds the DNA chain, recompressing it when the process is complete. The unwind-rewind cycle is repeated continuously throughout a cell's life.

In this study, Cairns and Clapier focused on assembly CRCs. "Before this research, we thought that the motor was off unless a protein coming from another part of the cell turned it on," said Cairns. "Researchers have been searching for the switch by looking at the CRC motor to see what binds to it.

"As it turns out, we discovered that the CRC motor already carries on its flank a 'switch' that inhibits its action until a marker sequence, located on the nucleosome, is encountered. The marker flips the inhibitor switch and allows the CRC to crank the DNA chain back around the nucleosome, promoting gene packaging and silencing" Cairns said. "Our results change where future researchers should be looking to understand how CRCs are regulated -- not at the CRC motor itself, but at the 'switches' that flank the motor."

The study also describes a measuring function on the CRC that checks for the correct distance between one nucleosome and the next, telling the motor to switch off at the proper time, a function needed for gene silencing.

Cairns's lab will now examine this same switching concept in disassembly remodelers. "There are additional remodeler families with alternative functions, like DNA repair," said Cairns. "We think this concept will apply to them as well."

This research was supported by funding from the National Institutes of Health (GM60415 and CA042014) and from the Howard Hughes Medical Institute.

Journal Reference:

1.      Cedric R. Clapier, Bradley R. Cairns. Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes. Nature, 2012; DOI: 10.1038/nature11625

Source:

The above story is reprinted from materials provided by University of Utah Health Sciences.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Eagle Group or its staff.

 

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