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A potential approach to treatment of hepatitis B virus infection
September 10, 2008Eukaryotic cells employ multiple strategies of checkpoint signaling and DNA repair mechanisms to monitor and repair damaged DNA. There are two branches in the checkpoint response pathway-ataxia telangiectasia-mutated (ATM) and ATM-Rad3-related (ATR). Many viruses are now known to interact with DNA damage sensing and repair machinery. These viruses have evolved tactics to eliminate, circumvent, or exploit various aspects of the DNA damage response of the host cell. Strategies include the activation of repair proteins or the targeting of specific cellular factors for degradation or mislocalization. Exploiting the activation of the DNA damage pathway by viral replication for the generation of antiviral drugs needs to be examined. In the human immunodeficiency virus (HIV), it has been clearly determined that the prevention of viral integration inhibits viral replication and promotes cellular apoptosis. Thus, the ATM-specific inhibitor ku55933 can inhibit HIV replication in primary T cells.
Despite the availability of a safe and efficient vaccine, chronic hepatitis B virus infection remains a major health problem worldwide. Interferon treatment is effective in only approximately one-third of the patients and produces considerable side effects. Long-term treatment with the second-generation nucleoside analogue lamivudine (lam) efficiently inhibits HBV replication with frequent viral polymerase mutations. We found that HBV infection triggered an ATR-dependent DNA damage response, resulting in increased ATR and Chk1 phosphorylation levels, however, ATR checkpoint signaling was blocked downstream of the p53-dependent pathway to evade apoptosis by p21 degradation. We have designed a strategy to select new drug targets that inhibit a cellular gene required for HBV replication or restore a response stalled by HBV in the ATR DNA damage pathway.
A research article to be published on August 28, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Professor, Zhong from Beijing Institute of Biotechnology used report that HBV infection activates and exploits the DNA damage response to replication stress. They investigated whether the inhibition of DNA damage response by CF, TP and UCN01 or the restoration of p21 expression by p21 transfection or proteasome inhibition would lead to suppressed HBV replication. They set up a chronic HBV infection model by culturing hepatocyte HL7702 cells with HBV-positive serum without washing off input virus as conventional. HBV DNA titers inside the infected cells represent the final viral amount including the infected DNA without being degraded and the newly synthesized HBV DNA. In this way, studying the efficacy of DNA damage response inhibitors on HBV infection and replication was available. In addition, since DNA damage response is an acute response that happens quickly after virus infection, they assume that early intervention of DNA damage pathway will function more efficiently, thus can be used clinically as HBV infection therapy during its early infectious stage or fulminant HBV infection.
World Journal of Gastroenterology
World Journal of Gastroenterology
Dna Damage Current Events and Dna Damage News RSSResearchers use drug-radiation combo to eradicate lung cancer
Researchers at UT Southwestern Medical Center have eliminated non-small cell lung (NSCL) cancer in mice by using an investigative drug called BEZ235 in combination with low-dose radiation.
Common weed could provide clues on aging and cancer
A common weed and human cancer cells could provide some very uncommon details about DNA structure and its relationship with telomeres and how they affect cellular aging and cancer, according to a team led by scientists from Texas A&M University and the University of Cincinnati (UC).
October 15, 2009 Loss of Tumor-Suppressor and DNA-Maintenance Proteins Causes Tissue Demise, Penn Study Finds
A study published in the October issue of Nature Genetics demonstrates that loss of the tumor-suppressor protein p53, coupled with elimination of the DNA-maintenance protein ATR, severely disrupts tissue maintenance in mice. As a result, tissues deteriorate rapidly, which is generally fatal in these animals. In addition, the study provides supportive evidence for the use of inhibitors of ATR in cancer therapy.
Heat forms potentially harmful substance in high-fructose corn syrup
Researchers have established the conditions that foster formation of potentially dangerous levels of a toxic substance in the high-fructose corn syrup (HFCS) often fed to honey bees.
Researcher Solves Mystery about Proteins that Package the Genome
A Florida State University College of Medicine researcher has solved a century-old mystery about proteins that play a vital role in the transfer of the human genetic code from one cell to another. The discovery could lead to finding new ways to help the body fight a variety of diseases, including cancer.
OU Part of International Study on Genetic Impact of Radiation
Researchers at the University of Oklahoma Health Sciences Center are helping to lead a massive international study on the possible genetic effects of radiation and cancer drug exposures on future generations.
Reactive oxygen in fruit flies acts as a cell signalling mechanism for immune response
For years, health conscious people have been taking antioxidants to reduce the levels of reactive oxygen in their blood and prevent the DNA damage done by free radicals, which are the result of oxidative stress. But could excessive use of antioxidants deplete our immune systems?
Identification of highly radiosensitive patients may lead to side effect-free radiotherapy
An international group of scientists has taken the first step on the road to targeting radiotherapy dosage to individual patients by means of their genetic characteristics.
Cancer Predisposition From Gene Variant Shows Strong Gender Bias
Cancer predisposition resulting from the presence of a specific gene variant shows a strong gender bias, researchers at the University of Cincinnati (UC) have demonstrated.
New vitamin K analysis supports the triage theory
An important analysis conducted by Children's Hospital Oakland Research Institute scientists suggests the importance of ensuring optimal dietary intakes of vitamin K to prevent age-related conditions such as bone fragility, arterial and kidney calcification, cardiovascular disease, and possibly cancer.
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Free-Radical-Induced DNA Damage and Its Repair: A Chemical Perspective by Clemens von Sonntag (Author) Understanding of the molecular basis of DNA damage and its repair has increased dramatically in recent years, and substantial knowledge now exists concerning the products arising from free-radical attack on DNA. Free-radical DNA damage may lead to mutations, cancer, and cell death. Free radicals have various sources, notably ionizing radiation and oxidative stress. In radiotherapy for cancer and with some anticancer drugs, use is made of cell death by excessive DNA damage. The mechanisms leading to products of free-radical attack which have been studied in models and with small double-stranded DNA fragments are discussed in detail, and the basics of the underlying free-radical chemistry are dealt with in separate chapters. |
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Demon Seduction Starring: Demon Seduction Directed By: Greg Lewolt An epic and bloody battle for the survival of planet Earth is on. Scientists experiment on a synthesized human-alien hybrid with new advanced DNA. A dying race of aliens must have the Super-DNA to continue building their population and they will stop at nothing to get it. Not wanting to bring attention to their mission, they morph into human females to seduce the scientists and obtain the secret formula. But if hot love making doesn t get the job done, the aliens will start gruesome, gut-ripping carnage and destroy all of man-kind. |
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***** Biotivia Derma Pearl ***** Trans Resveratrol Anti-Aging Beauty Skin Treatment Cream ~ 1st Anti-Aging Cosmeceutical that operates at the DNA level! Permanently reverse the signs of aging & protect against FUTURE damage ***** by Biotivia In one month of daily use you will experience a profound improvement in skin quality that no other natural or prescription product can replicate. You have nothing to lose but your wrinkles. Primary cause of skin aging and damage is the accumulation of DNA errors due to radiation from the sun, oxidative stress from energy production at the mitochrondria level, environmental toxins, less than perfect diet and stresses we all experience from lifestyle. By enhancing the body's natural DNA repair mechanisms can this damage be reversed and new damage prevented. Resveratol is one of very few compounds that have been shown to up molulate DNA repair in mamallian cells. This genetic approach represents a revolution in anti-aging skin care treatments. Until now all so-called anti-aging creams and... |
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DNA Damage and Repair: Volume II: DNA Repair in Higher Eukaryotes (Contemporary Cancer Research) by Jac A. Nickoloff (Editor), Merl F. Hoekstra (Editor) Univ. of New Mexico, Albuquerque., Critical review of all major aspects of DNA repair in a wide variety of organisms. Topics include UV and X-ray repair, repair of chemical damage, and the role of DNA repair in disease prevention. For researchers. Complete in two volumes. DNLM: DNA Repair. |
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Technologies for Detection of DNA Damage and Mutations by G.P. Pfeifer (Editor) ''Useful and timely.'' ---Mutagenesis ''Of considerable value.'' ---Journal of Medical Genetics ''Quite readable....a comprehensive overview....perfectly covers the needs of those researchers who have to decide on the best strategy to identify damage or mutations at the molecular level.'' ---Trends in Cell Biology ''The formats of the presentations are uniform and ample and up-to-date references are provided at the end of each chapter...will be welcomed by postgraduate researchers of all ages and should retain its usefulness for a long time.'' ---Endeavour, 21(4), 1997 This important resource thoroughly reviews a wide range of techniques used in mutagenesis research--ranging from established techniques to recently developed methodologies--based on the polymerase chain... |
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DNA Damage Recognition by Wolfram Siede (Editor), Yoke Wah Kow (Editor), Paul W. Doetsch (Editor) Stands as the most comprehensive guide to the subject—covering every essential topic related to DNA damage identification and repair. Covering a wide array of topics from bacteria to human cells, this book summarizes recent developments in DNA damage repair and recognition while providing timely reviews on the molecular mechanisms employed by cells to distinguish between damaged and undamaged sites and stimulate the appropriate repair pathways. about the editors... WOLFRAM SIEDE is Associate Professor, Department of Cell Biology and Genetics, University of North Texas Health Science Center, Fort Worth. He received the Ph.D. degree (1986) from Johann Wolfgang Goethe University, Frankfurt Germany. YOKE WAH KOW is Professor, Department of Radiation Oncology, Emory... |
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Progress in DNA Damage Research by Souta Miura (Editor), Shouta Nakano (Editor) This book presents the latest research on DNA damage, which due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 1,000 to 1,000,000 molecular lesions per cell per day. While this constitutes only 0.000165 per cent of the human genome's approximately 6 billion bases (3 billion base pairs), unrepaired lesions in critical genes (such as tumour suppresser genes) can impede a cell's ability to carry out its function and appreciably increase the likelihood of tumour formation.The vast majority of DNA damage affects the primary structure of the double helix; that is, the bases themselves are chemically modified. These modifications can in turn disrupt the molecules' regular helical structure by introducing non-native chemical bonds or bulky adducts... |
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The DNA Damage Response: Implications on Cancer Formation and Treatment by Kum Kum Khanna (Editor), Yosef Shiloh (Editor) The book The DNA Damage Response: Implications on Cancer Formation and Treatment brings together a great collection of review articles. The articles have been written by a group of experts who have a deep knowledge of the recent advances in the fields of DNA damage signalling and repair and their implications in carcinogenesis. The book is divided into chapters that deal with the elaborate surveillance system and repair mechanisms used by cells to suppress mutagenic lesions to avoid cancer. It provides snapshots of: |
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DNA Damage and Repair: Volume I: DNA Repair in Prokaryotes and Lower Eukaryotes (Contemporary Cancer Research) by Jac A. Nickoloff (Editor), Merl F. Hoekstra (Editor) Univ. of New Mexico, Albuquerque. Volume 1 of a 2-volume set presenting a critical review of major aspects of DNA repair in a wide variety of organisms. Illustrated. Outline format. DNLM: DNA Repair. |
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New Research on DNA Damage by Honoka Kimura (Editor), Aoi Suzuki (Editor) DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 1,000 to 1,000,000 molecular lesions per cell per day. While this constitutes only 0.000165 per cent of the human genome's approximately 6 billion bases (3 billion base pairs), unrepaired lesions in critical genes (such as tumour suppresser genes) can impede a cell's ability to carry out its function and appreciably increase the likelihood of tumour formation.The vast majority of DNA damage affects the primary structure of the double helix; that is, the bases themselves are chemically modified. These modifications can in turn disrupt the molecules' regular helical structure by introducing non-native chemical bonds or bulky adducts that do not fit in the standard double helix.... |
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