Information on DNA and Wellness and their connection
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Researchers Find New Way To Study How Enzymes Repair DNA Damage
Posted on January 28th, 2010 No commentsJanuary 28, 2010
Researchers at Ohio State University have found a new way to study how enzymes move as they repair DNA sun damage — and that discovery could one day lead to new therapies for healing sunburned skin.
Ultraviolet (UV) light damages skin by causing chemical bonds to form in the wrong places along the DNA molecules in our cells. Normally, other, even smaller molecules called photolyases heal the damage. Sunburn happens when the DNA is too damaged to repair, and cells die.
Photolyases have always been hard to study, in part because they work in tiny fractions of a second. In this week’s online edition of the Proceedings of the National Academy of Sciences, Ohio State physicist and chemist Dongping Zhong and his colleagues describe how they used ultra-fast pulses of laser light to spy on a photolyase while it was healing a strand of DNA.
This is the first time that anyone has observed this enzyme motion without first attaching a fluorescent molecule to the photolyase, which disturbs its movements. They were able to see the enzyme’s motion to help the healing process as it happens in nature.
“Now that we have accurately mapped the motions of a photolyase at the site of DNA repair, we can much better understand DNA repair at the atomic scale, and we can reveal the entire repair process with unprecedented detail,” said Zhong, the Robert Smith Associate Professor of Physics, and associate professor in the departments of chemistry and biochemistry at Ohio State.
Such small motions are very hard to study. Typically, researchers deal with the problem by attaching tiny bits of fluorescent molecules to the enzymes they are trying to study. But adding an extra molecule to an enzyme such as photolyase could change how it moves.
“Once you tag it, you can’t be sure that the motions you detect are the true motions of the molecule as it would normally function,” Zhong explained.
So instead of using tags, he and his team took laser “snapshots” of a single photolyase in action in the laboratory. They mapped the shape and position of the photolyase molecule as it broke up the harmful chemical bonds in DNA caused by UV light. The whole reaction lasted only a few billionths of a second.
In nature, DNA avoids damage by converting UV rays into heat. Sunscreen lotions protect us by reflecting sunlight away from the skin, and also by dissipating UV as heat.
Sunburn happens when the DNA absorbs the UV energy instead of converting it to heat. This is due in part to the random position of the DNA molecule within our cells when the UV hits it. When the UV energy is absorbed, it triggers chemical reactions that form lesions — errant chemical bonds — along the DNA strand.
If photolyases are unable to completely repair the lesions, the DNA can’t replicate properly. Badly damaged cells simply die — that’s what gives sunburn its sting. Scientists also believe that chronic sun damage creates mutations that lead to diseases such as skin cancer.
The work in Zhong’s lab is fundamental to the understanding of how those molecules interact. Other researchers could use this information to design drugs to heal sun damage.
“Of course, the ultimate goal of studying DNA repair is to help design artificial systems to mimic it,” he said.
More information: http://www.pnas.org/
Provided by The Ohio State University (news : web)
DNAWellnessinfo.com Resource: http://www.physorg.com/news183913344.html
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Molecular Security System That Protects Cells from Potentially Harmful DNA Discovered
Posted on January 14th, 2010 No commentsScienceDaily (Jan. 14, 2010) — Researchers at the University of Minnesota have discovered a molecular security system in human cells that deactivates and degrades foreign DNA. This discovery could open the door to major improvements in genetic engineering and gene therapy technologies.
Led by Reuben Harris, associate professor of biochemistry, molecular biology and biophysics in the College of Biological Sciences, the report’s findings will be published online by Nature Structural and Molecular Biology on Jan. 10.
In the study, Harris and colleagues show how APOBEC3A, an enzyme found in human immune cells, disables double-stranded foreign DNA by changing cytosines (one of the four main bases in DNA) to uracils (an atypical DNA base). Persisting DNA uracils result in mutations that disable the DNA. In addition, the authors show that other enzymes step in to degrade the uracil-containing foreign DNA and sweep its remains out of the cell.
“Scientists have known for a long time that some human cells take up DNA better than others, but we haven’t had good molecular explanations,” Harris says. “This is definitely one of the reasons. Foreign DNA restriction is a fundamental process that could have broad implications for a variety of genetic diseases.”
By understanding how the mechanism works, scientists can develop ways to manipulate it to enable more effective methods to swap bad genes for good ones. Harris is also intrigued to learn why the mechanism doesn’t affect a cell’s own DNA.
The discovery of an analogous foreign DNA restriction mechanism in bacteria launched the field of genetic engineering during the 1970s. Once bacterial DNA restriction enzymes were understood, their power was harnessed to cut and paste segments of DNA for a wide variety of therapeutic and industrial purposes.
DNAWellnessinfo.com Resource: http://www.sciencedaily.com/releases/2010/01/100110151321.htm
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New Molecule Identified in DNA Damage Response
Posted on January 1st, 2010 1 commentScienceDaily (Jan. 1, 2010) — In the harsh judgment of natural selection, the ultimate measure of success is reproduction. So it’s no surprise that life spends lavish resources on this feat, whether in the courtship behavior of birds and bees or replicating the cells that keep them alive. Now research has identified a new piece in an elaborate system to help guarantee fidelity in the reproduction of cells, preventing potentially lethal mutations in the process.
n experiments to be published in the December 18 issue of the Journal of Biological Chemistry, researchers at The Rockefeller University identified the molecule SMARCAL1 as part of cells’ damage control response to malfunctioning DNA replication. In typical cell division, many different molecules have roles in guaranteeing the daughter strands of DNA are as identical as possible to their parent. Some molecules check for errors or ‘proofread’ the offspring for typos, for instance; others, when alerted to a problem, arrest the replication process and conduct repairs.
Lisa Postow, a postdoctoral fellow in Hironori Funabiki’s Laboratory of Chromosome and Cell Biology, used mass spectroscopy to identify SMARCAL1 as involved in this intricate quality control process. Working with Brian T. Chait’s Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Postow found the protein in a proteomics screen for molecules that were drawn to a dangerous DNA repair problem called a double-strand break.
In both human cells and in cells from African clawed frog egg extract, Postow found that at double-strand breaks, SMARCAL1 gathered with another molecule called RPA, which is known to coat broken strands of DNA and protect them while damage is repaired. SMARCAL1 had an added interest, too: A mutation in the gene that produces it is involved in a rare but lethal disease called Schimke immuno-osseous dysplasia, a disorder that causes wide-ranging problems including kidney malfunction, immunodeficiency and growth inhibition.
To Postow’s surprise, she found that removing SMARCAL1 had little effect on double-strand break repair. However, it did facilitate a different aspect of the DNA damage response called replication fork stabilization, a process that holds steady the junction between parental and daughter strands — the replication fork — when replication is stalled because a problem has been detected. “For a mutation that causes such wide-ranging and severe physiological effects, it is surprising that the protein has such a relatively small effect at the cellular level,” Postow says.
Postow’s findings were largely corroborated by independent new research into SMARCAL1, which was published this fall in four back-to-back papers in Genes & Development. The work reveals another piece of the complex safeguards the body has in place to protect against dangerous mutations.
“This study also proves that the proteomic approach that Lisa has developed with Dr. Chait can efficiently identify proteins involving the DNA-damage recognition and repair process,” says Funabiki. “Many more excitements are ahead of us.”
DNAWellnessinfo.com Resource: http://www.sciencedaily.com/releases/2009/12/091231152519.htm
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New Study Links Child Abuse, DNA Damage
Posted on December 26th, 2009 1 commentdigitaljournal.com
Dec 26, 2009 by ? Martin Laine
Beyond the psychological and emotional stress of childhood abuse and neglect, a Brown University study shows a link with damage to victims’ DNA in later life.The study, published in October in the journal Biological Psychiatry, examined the DNA of 31 adults who had reported experiencing maltreatment as children, but who had not been diagnosed with any major psychiatric disorders. The researchers found that their subjects had shortened telomeres on their DNA strands, shorter than those found in otherwise similar adults who did not experience childhood mistreatment. Telomeres are the “end-caps” of DNA strands, and their shortening is an indication of advanced cell aging. The study is yet further evidence that child abuse and neglect can have far-reaching effects on an individual, all the way down to the cellular level. “When we looked at childhood maltreatment over all, including all types of abuse or neglect, we found it reverberating to the cellular effect and this very basic cellular mechanism,” said Dr. Audrey Tyrka, of Butler Hospital and Brown University, one of the authors of the study, in an interview with the Providence Journal. Earlier research has shown that such conditions as heart disease, cancer, and excessive stress can cause telomere shortening, which has serious implications to an individual’s health. “Telomere length is critical to protecting the cell,” Dr. Tyrka said. “When telomeres shorten too much, the cell stops replicating. The cell may die or there may be genetic abnormalities that result within the cell. A Canadian study published in February in the journal Nature Neuroscience found that victims of child abuse had different epigenetic markings in that part of the brain that influences an individual’s stress-response. Researchers at McGill University and the Douglas Mental Health University Institute in Montreal studied the brains of suicide victims who were known to have suffered child abuse. “We know from clinical experience that a difficult childhood can have an impact on a person’s life,” said Prof. Moshe Szyf, one of the researchers, in an article in Medical News Today. ”Now we are starting to understand the biological implications of such psychological abuse.”DNAWellnessinfo.com Resource: http://www.digitaljournal.com/article/284493 -
Breast cancer is not a single disease, scientists discover
Posted on December 24th, 2009 2 commentsFrom The TimesDecember 24, 2009Mark Henderson, Science EditorBreast cancer is not a single disease but a collection of at least five separate conditions that differ in prognosis and response to treatment, a detailed genetic study has revealed.
A comparison of the genomes of 24 breast tumours has found several distinct patterns of DNA damage, each of which appeared to be characteristic of a peculiar sub-type of cancer.
The findings, from a British team that unveiled last week the first comprehensive genetic maps of two tumours, offer insights into the biology of breast cancer that promise improvements to diagnosis and treatment.
As more is understood of the genetic architecture of different kinds of breast cancer, scientists expect to be able to classify patients’ tumours according to their DNA signatures.
This information could then be used by doctors to establish how aggressive the tumour will be, and which therapy is most likely to work.
Mike Stratton, of the Cancer Genome Project at the Wellcome Trust Sanger Institute, said: “There is massive diversity between individual breast cancers and it is quite clear that these 24 tumours are not all examples of the same disease.
“As time goes on, we are becoming increasingly aware that breast cancer is very biologically diverse. Our work supports the view that breast cancer is not one but several diseases.
“If this diversity is associated with a different prognosis, or sensitivity to drugs, it will become very useful on a clinical level.”
Oncologists already recognise that there are three to four broad groups of breast cancers, which differ in their responses to particular drugs.
Herceptin (trastuzumab), for example, works only against tumours that are positive for a receptor called HER-2, while tamoxifen is effective only when cancer cells have a receptor for the female hormone oestrogen.
There are also “triple-negative” cancers that lack receptors for HER-2, oestrogen and progesterone, which are often particularly aggressive and difficult to treat.
Professor Stratton’s study, which is published in the journal Nature, has identified genetic profiles characteristic of each of these groups, along with several others that suggest that these classes can be subdivided still further.
“It’s already understood that breast cancer is at least three to four different animals,” Professor Stratton said.
“The genetic architecture suggests that we’re probably going to be dealing with at least five to ten different animals. It’s clear that the triple-negative cancers, for example, are clearly going to subdivide into multiple different categories.”
In the study, the scientists examined 24 tumours for evidence of rearrangements — a type of genetic damage in which large chunks of chromosomes break off and reattach themselves in unusual ways.
It revealed great differences between one tumour and another: while some tumours were relatively undisturbed, others were chaotic with more than 200 rearrangements.
“We were, frankly, astounded at the number and complexity of rearrangements in some cancers,” Professor Stratton said.
The research comes a week after his team published the first comprehensive catalogues of all the mutations present in two cancer genomes, of a lung tumour and a melanoma.
The breast cancer study has not yet investigated the disease in this exhaustive detail, but a project is under way to do this for 1,500 breast tumours, under the £600 million International Cancer Genome Consortium.
“When we are a fair way into this, we will have a clearer idea of how many well-defined sub-types of breast cancer there are,” Professor Stratton said.
“Once we have pinned that down, we will need to look at this in the context of clinical progression, to see what is useful to look at in patients.
“The aim is to identify cancer-causing genes that are produced by these rearrangements, and to develop therapies that target them,” Professor Stratton said.
Jorge Reis-Filho, of the Breakthrough Breast Cancer Research Centre at the Institute of Cancer Research in London, another member of the research team, said that the study suggested that faulty DNA repair mechanisms underlay rearrangements in breast cancer.
“It appears that in different sub-types of breast cancers, distinct mechanisms of DNA repair are impaired, leading to different types of genomic disorganisation,” he said.
“If we damage further an already faulty DNA repair system using tailored therapies, one can kill tumour cells selectively, without harming normal cells.
“There are already some highly interesting results suggesting that breast cancers with defects in DNA repair are more sensitive to drugs that cause additional DNA damage.”
New drug offers hope against Ewing’s sarcoma
A new drug may halt the growth of a rare form of cancer that mainly affects teenage boys, scientists say (David Rose writes).
An early study of the drug figitumumab has found that it can be an effective treatment for Ewing’s sarcoma, which forms in the bones of about 30 young people in Britain each year.
The promising results, published online in the Lancet Oncology journal, come from a study on 29 patients which aimed to check whether figitumumab was safe for sarcoma patients.
The trial covered a range of relatively uncommon cancers that form in the bones or soft tissues of the body.
The average age of patients in the trial was 30, but all had advanced cancers that were responding poorly to existing treatments such as chemotherapy and radiotherapy.
But figitumumab was shown to be effective for at least 16 patients with Ewing’s sarcoma, which is typically diagnosed between the ages of 10 and 20, and more commonly affects boys than girls.
DNAWellnessinfo.com Resource: http://www.timesonline.co.uk/tol/news/uk/article6966927.ece
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Cancer Researchers Focus On DNA Damage
Posted on December 17th, 2009 7 commentsPOSTED: 3:08 pm PST December 16, 2009
UPDATED: 8:33 am PST December 17, 2009BAKERSFIELD, Calif. — In the war on cancer, scientists are battling the disease right where it begins: within tiny strands of DNA. There are many different kinds of mutations in DNA that can cause cancer, and each specific change provides new clues about how the illness starts and potential ways to treat it. In two new studies, British researchers found evidence that our behavior alters some genes and these changes may trigger cancers.Doctors studying tumor cells from a man with melanoma found DNA damage caused by ultraviolet light — and UV rays from the sun are a known risk factor for skin cancer. Other research on lung cancer cells revealed mutations caused by carcinogens in tobacco smoke. Scientists saw evidence that the DNA had tried to repair itself but it was unsuccessful. Experts said these findings show the interplay between our genes and our environment — people are born with risks for certain diseases due to their genes, but then their lifestyle choices act on those same genes, changing them for the better or the worse.Report a typo or inaccuracyCopyright 2009 by TurnTo23.com. The Associated Press contributed to this report. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
DNAWellnessinfo.com Resource: http://www.turnto23.com/health/21986351/detail.html
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