April 11, 2010- physorg.com

Scientists have shown in multiple contexts that DNA damage over our lifetimes is a key mechanism behind the development of cancer and other age-related diseases. Not everyone gets these diseases, because the body has multiple mechanisms for repairing the damage caused to DNA by aging, the environment and other human behaviors – but the mechanisms behind certain kinds of DNA repair have not been well-understood.

In a paper published today in the journal Nature, researchers at the University of North Carolina at Chapel Hill’s Lineberger Comprehensive Cancer Center have shown that a particular protein – called Ku – is particularly adept at healing damaged strands of DNA.

According to Dale Ramsden, PhD, associate professor in the department of biochemistry and biophysics and a member of the curriculum in genetics and molecular biology, Ku is a very exciting protein because it employs a unique mechanism to repair a particularly drastic form of DNA damage.

“Damage to DNA in the form of a broken chromosome, or double strand break, can be very difficult to repair – it is not a clean break and areas along the strand may be damaged at the level of the fundamental building blocks of DNA – called nucleotides,” he notes.

Broken chromosomes can be compared to a break in a strand of yarn made up of several different threads or plies. Unless scissors are used to cut the yarn, the strand frays and may break or be damaged at several different places up and down the length of the yarn. These rough ends get “dirty” – making them harder to repair.

Provided by University of North Carolina

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Key protein aids in DNA repair is a post from: dnawellnessinfo.com

Naveen Kumar, TNN, Mar 6, 2010, 10.23pm IST

VARANASI: Now, the study of DNA repairing gene using single nucleotide polymorphism (SNP) marker would provide vital cue for cancer prevention, especially neck and head that comprises of as many as seven different types of cancer in the facial region. In addition, the study would also enable early prediction of much feared breast cancer in women.

While a team of scientists is studying the genomics in cancer, especially the squamous cell carcinoma in neck, head and breast region under the Hap Map project, the case studies in the last five years have revealed interesting contribution of DNA repairing genes including P53 associated genes, where SNP can be used as a marker for prompt diagnostic purpose.

Senior scientist Central Drug Research Institute Lucknow Dr SK Rath told TOI on Saturday, “The studies have shown that P53 associated genes play a vital role in DNA repair and act as tumour suppressor. It changes the DNA repair scene and plays pivotal role in protection against mutagenic and cytotoxic effects of DNA damage that also prevents cancer.” Similarly, SNP could also provide vital cue for DNA repairing in BRAC 1 and 2 genes that are believed to cause breast cancer in women, he added.

It is to be mentioned here that Dr Rath is a key member of the team that studied genotype of cancerous and non-cancerous cells under the project in the Xth five-year plan. Now, the team is researching on SNP of different people including smokers and non-smokers, drinkers and non-drinkers, where the cause of cancer

could not be ascertained.

Saying that million of SNPs exist in human genome that occur in gene within the regulatory region, Dr Rath emphasised that the method detects the most common type of variation in the genome, as it cater to small alteration, providing better scope for prediction. The SNP markers are preferred for population genomic disease association and are good indicators of squamous cell carcinoma in neck and head region that includes cancers of oral cavity, pharynx, nasopharynx, oropharynx, hypopharynx and tongue, he added.

Stressing that cancers of neck and head region are growing at alarming rate in states like UP, he said the case studies in Lucknow revealed that out of 100 cancer patients, the number of patients with cancer in the neck and head region increased from 30 to 49 (150 per cent increase) in the last five years. Worldwide, it is the fifth most common type of cancer affecting over one million population annually, he concluded.

DNAWellnessinfo.com Resource:  http://timesofindia.indiatimes.com/city/varanasi/-Vital-cues-for-cancer-prevention-through-DNA-repairing-gene/articleshow/5648729.cms

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January 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.

More information: http://www.pnas.org/

Provided by The Ohio State University (news : web)

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ScienceDaily (Dec. 3, 2009) — A protein that plays a key role in copying DNA also plays a vital role in repairing breaks in it, UC Davis scientists have found. The work is helping researchers understand how cancer cells can resist radiation and chemotherapy, as well as how cells become cancerous in the first place.

The protein, known as proliferating cell nuclear antigen, forms a ring that fits around the DNA double helix. This cuff-like ring helps to keep in place DNA polymerase, the enzyme that makes a copy of the DNA strand when cells divide into two new cells.

The new study, published Nov. 25 in the journal Molecular Cell, shows that PCNA performs a similar function during DNA recombination — when pairs of chromosomes line up and exchange strands of DNA. Recombination occurs when cells divide to form eggs and sperm, and also when cells try to repair breaks that cross both strands of DNA.

“This is a new trick from an old horse,” said Wolf-Dietrich Heyer, professor of microbiology at UC Davis and leader of the molecular oncology program at the UC Davis Cancer Center.

The system developed by Heyer and colleagues for their experiments, using defined DNA substrates and purified proteins in a test tube, can be used to investigate the behavior of other molecules involved in copying and repairing DNA as well, he said.

Heyer’s lab works primarily with yeast. While yeast don’t get cancer, Heyer notes that their DNA recombination and repair machinery is essentially the same as in humans. This problem was solved by evolution a long time ago, he said.

Radiation therapy and cancer drugs both cause breaks in cancer cells’ DNA. Create enough breaks, and the malignant cell dies — but at the same time, the cell’s repair machinery is at work patching and sealing the gaps.

Understanding how DNA recombination and repair work could open up ways to make tumors more vulnerable to treatment, or to predict how well patients will fare with a specific treatment. The research could also reveal genes that predispose some people to cancer. For example, the “breast cancer gene,” BRCA-2, is involved in DNA repair.

“We now know a lot about the molecules involved in DNA repair; we’re beginning to think about how they can be used in the clinic,” Heyer said.

Co-authors of the study were UC Davis graduate student Xuan Li, now a postdoctoral fellow at Harvard Medical School; and research lab supervisor Carrie Stith and Professor Peter Burgers, both of the Department of Biochemistry and Molecular Biophysics at Washington University School of Medicine in St. Louis. The work was funded by the National Institutes of Health.

DNAWellnessinfo.com Resource:  http://www.sciencedaily.com/releases/2009/12/091203171716.htm

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12/2/2009 9:44:00 AM naturalproductsinsider.com

Results from a recent study suggest interactions among zinc deficiency, DNA integrity, oxidative stress and DNA repair and suggested a role for zinc in maintaining DNA integrity (J Nutr. 2009;139(9):1626-31). Sprague-Dawley rats were fed zinc-adequate (ZA; 30 mg Zn/kg) or severely zinc-deficient (ZD; less than 1 mg Zn/kg) diets or were pair-fed zinc-adequate diet to match the mean feed intake of ZD rats for three weeks. After zinc depletion, rats were repleted with a ZA diet for 10 days. In addition, zinc-adequate (MZA 30 mg Zn/kg) or marginally zinc-deficient (MZD; 6 mg Zn/kg) diets were given to different groups of rats for six weeks. Severe zinc depletion caused more DNA damage in peripheral blood cells than in the ZA group and this was normalized by zinc repletion. Researchers also detected impairments in DNA repair, such as compromised p53 DNA binding and differential activation of the base excision repair proteins 8-oxoguanine glycosylase and poly ADP ribose polymerase. MZD rats also had more DNA damage and higher plasma F(2)-isoprostane concentrations than MZA rats and had impairments in DNA repair functions. However, plasma antioxidant concentrations and erythrocyte superoxide dismutase (SOD) activity were not affected by zinc depletion.

DNAWellnessinfo.com Resource:  http://www.naturalproductsinsider.com/news/2009/12/zinc-and-dna-integrity.aspx

DNA Guided Nutrition:  http://www.dnaguidedwellnessproducts.com

Zinc and DNA Integrity is a post from: dnawellnessinfo.com

ScienceDaily (Oct. 22, 2009) — Researchers report that a single-stranded DNA-binding protein (SSB), once thought to be a static player among the many molecules that interact with DNA, actually moves back and forth along single-stranded DNA, gradually allowing other proteins to repair, recombine or replicate the strands.

single-stranded DNA-binding protein (SSB)

Single-stranded DNA-binding Protein Is Dynamic, Critical To DNA Repair is a post from: dnawellnessinfo.com