DNA Surveillance and Repair
Chapters
page 1 of 2 pages | next »Analysis of 8-Hydroxy-2´-Deoxyguanosine as a Marker of Oxidatively Damaged DNA in Relation to Carcinogenesis and Aging
H. Kasai, T. Hirano, K. Kawai, Y. Tsurudome, H. Itoh, D. Himeji and T. Horiuchi
Reactive oxygen species (ROS) are well known hazards for living organisms and are believed to be associated with the induction of cancer. ROS induce many forms of oxidative damage to proteins, nucleic acids, and lipids. Therefore, to diagnose or prevent cancer, analyses of oxidative products i...
Animal Models of Xeroderma Pigmentosum
Xue-Zhi Sun, Rui Zhang, Chun Cui, Yoshi-Nobu Harada, Setsuji Hisano, Yeunhwa Gu, Yoshihiro Fukui and Hidenori Yonehara
Xeroderma pigmentosum (XP) is a rare autosomal disorder characterized by hypersensitivity of the skin to sunlight specifically to ultraviolet (UV) which can lead to high rate of susceptibility to skin cancer and other kinds of neurodegenerative problems. Compared to normal individuals, XP patients h...
Cell Cycle Defects and Apoptosis in Ataxia telangiectasia
Deborah Wilsker and Fred Bunz
ATM is a key regulator of both cell cycle checkpoints and apoptosis. Cells lacking ATM are defective in critical responses to damaged DNA and particularly to the double strand DNA breaks caused by ionizing radiation (IR). Depending on the cell type, ATM‑deficient cells are extremely sensitive ...
Cell Signaling in Ataxia Telangiectasia
Tetsuo Nakajima
Ataxia-telangiectasia (AT) is a disease with pleiotropic defects that include hypersensitivity to ionizing radiation, immunodeficiency and increased cancer risk and Ataxia Telangiectasia Mutated (ATM) gene is responsible for AT. Particularly since AT patients are strongly radiosensitive, the relatio...
Chlorination and Nitration of DNA and Nucleic Acid Components
Clare L. Hawkins, David I. Pattison, Matthew Whiteman and Michael J. Davies
Activated phagocytes generate a complex mixture of oxidants that are believed to be crucial to bacterial cell killing. However, excessive or misplaced generation of these oxidants is known to damage host tissue. This damage is understood to be important in a number of diseases, and considerabl...
Chromosomal Instability in Ataxia Telangiectasia
Luitpold V. Distel
Ataxia telangiectasia (AT) is a syndrome with multiple symptoms, of them one is the frequent and early onset of cancer. The disease is triggered by a mutation in the ATM‑gene. The gene and its encoded protein, with 3056 amino acids, have different domains and functions. It plays a central role...
Clinical Features of Xeroderma Pigmentosum
Ulrich R. Hengge and Steffen Emmert
Xeroderma pigmentosum (XP) was first described in 1874 by Hebra and Kaposi. Albert Neisser was the first to report neurological abnormalities associated with XP in 1883. XP is an autosomal recessive disease with defective nucleotide excision repair (NER). It is characterized by easily recognizable c...
DNA Damage and Repair in Ataxia Telangiectasia
Melissa M. Adams and Phillip Carpenter
Defects in the gene Ataxia Telangiectasia Mutated (ATM) are responsible for the development of Ataxia Telangiectasia (AT), an incurable cancer‑prone disease that is accompanied by a pleiotropic set of conditions including, amongst others, neurological and immunological deficiencies. ATM is a l...
Historical Aspects of Xeroderma pigmentosum and Nucleotide Excision Repair
James Cleaver
The discovery that xeroderma pigmentosum was a sun‑sensitive hereditary human disease that was deficient in DNA repair was made when research into the fundamental mechanisms of nucleotide excision repair was in its infancy. The linkage between DNA damage, DNA repair and human cancer stimulated...
Mammalian Base Excision Repair
Grigory L. Dianov, Sarah L. Allinson, Helen Budworth and Kate Sleeth
In living cells DNA base lesions are formed continuously as a consequence of normal me tabolism and are also generated by a number of external factors. Simple base damages are repaired by base excision repair that includes two major pathways. These two pathways involve different subsets of enzy...
Mammalian DNA Mismatch Repair
Helen M.R. Robinson and Robert Brown
Some DNA replication errors escape the proof reading activity of DNA polymerases and if allowed to persist will lead to mutations and potential creation of an abnormal mutant cell. Therefore such errors have to be repaired or the potentially abnormal cell needs to be eliminated. DNA mismatch r...
Nucleic Acid Oxidation and the Pathogenesis of Cardiovascular Diseases
Maria Grazia Andreassi
Cardiovascular disease is the dominant health problem in the western world. The most frequent underlying cause of cardiovascular disease is atherosclerosis. The cellular and molecular mechanisms involved in atherosclerosis and its acute complications are being defined, but much is still unknow...
Nucleotide Incision Repair: An Alternative and Ubiquitous Pathway to Handle Oxidative DNA Damage
Sophie Couvé-Privat, Alexander A. Ishchenko, Jacques Laval and Murat Saparbaev
Aerobic respiration and exogenous factors such as ionizing radiation and drugs generate reactive oxygen species (ROS). DNA has limited chemical stability and it is one of the most biologically important targets of ROS.1 Oxidative DNA lesions are believed to be a major type of endogenous damage...
OGG1: From Structural Analysis to the Knockout Mouse
Arne Klungland, Jon K. Laerdahl and Torbjørn Rognes
Among the four DNA bases, guanine, having the lowest redox potential, is the most susceptible to oxidation, and among the oxidized bases 7,8-dihydro-8-oxoguanine (8-oxoG) is certainly the lesion that has retained most attention over many years. This altered base can pair with A as well as C re...
Oncogenesis in Ataxia Telangectasia: Roles of Atm, p53, Nf‑kb and DDE recombination pathogenesis
David H. Dreyfus
The mechanistic basis of ATM (Ataxia Telangectasis Mutated) protein interactions with DNA hairpin and related double stranded DNA breaks, generated through V(D)J recombination, has been the subject of numerous recent experimental reports and reviews. The novel focus of this review is the potential s...
Origin, Recognition, Signaling and Repair of DNA Double-Strand Breaks in Mammalian Cells
Larry H. Thompson and Charles L. Limoli
Achromosomal double-strand break (DSB) can arise from multiple sources including ionizing radiation and DNA replication itself. An understanding of the intricate pro tein pathways that recognize DSBs and recruit the DNA repair and cell cycle checkpoint machinery is developing rapidly. The ATM k...
Other Proteins Interacting with XP Proteins
Steven M. Shell and Yue Zou
Genetic defects in Nucleotide excision repair (NER) lead to the clinical disorder Xeroderma pigmentosum (XP) in humans which is characterized by dramatically increased sensitivity to UV light and a predisposition to development of skin cancers.1,2 NER is a major mechanism of DNA repair in cells for ...
Oxidative Damage and Promoter Function
David Mitchell and Rita Ghosh
Evidence is accumulating that base damage, particularly that produced by oxidation reactions, can modulate DNA protein interactions and affect promoter function. Such lesions have the capacity to interfere with normal gene regulation through direct interactions with promoter elements, or indir...
Oxidative DNA Damage and Carcinogenesis
Ryszard Olinski, Marek Foksinski and Barbara Tudek
In living cells, there is a steady formation of DNA lesions. A substantial number of these lesions are formed by endogenous factors such as reactive oxygen species (ROS) that damage DNA on a continuous basis. Therefore, it is likely that ROS are the most important human carcinogens. An involv...
Oxidative DNA Damage and Telomere Shortening
Torsten Richter and Thomas von Zglinicki
Telomeres are highly complex DNA-protein structures that protect the ends of chromo- somes. A variety of DNA damage response and repair proteins are bound to telomeres and fulfil functions in the maintenance of the telomeric cap, in the protection of chromosomes from end-to-end fusion and, if t...
Oxidatively Damaged DNA and Inflammation
Peter Dedon and Marita C. Barth
Chronic inflammation has long been associated with diseases such as cancer and cardiovascular disease, with infectious processes playing a causal role in many types of cancer. One potential link between chronic inflammation and human disease involves the release of highly reactive oxygen and n...
Oxidatively Generated Damage to Cellular DNA: Mechanistic Aspects
Jean Cadet, Thierry Douki, Carine Badouard, Alain Favier and Jean-Luc Ravanat
In this chapter emphasis is placed on recent aspects of the oxidative formation of several classes of modified bases in cellular DNA that arise from the reaction of the hydroxyl radical (•OH), singlet oxygen and hypochlorous acid. Degradation compounds are detected quantitatively and specifica...
Population Distribution of Xeroderma Pigmentosum
Abdul Manan Bhutto and Sandra H. Kirk
Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disease caused by defects in the normal repair of DNA of various cutaneous and ocular cell types damaged by exposure to sunlight.1‑3 Hebra and Kaposi reported the disease initially in 1874.4 It generally shows early onset of symp...
Prevention of the Mutagenecity and Cytotoxicity of Oxidized Purine Nucleotides
Yusaku Nakabeppu, Mehrdad Behmanesh, Hiroo Yamaguchi, Daisuke Yoshimura and Kunihiko Sakumi
Damage to nucleic acids is particularly hazardous because the genetic information in genomic DNA, such as nuclear and mitochondrial DNA, can be altered. Damage accumulated in cellular DNAs often initiates programmed cell death, as well as mutagenesis. The former may cause degenerative diseases...
Processing of 3´-End Modified DNA Strand Breaks Induced by Oxidative Damage
Jason L. Parsons, Emma Boswell and Grigory Dianov
In living cells, the DNA molecule is subject to attack from reactive oxygen species generated as the result of endogenous oxidative metabolism and exogenous factors, such as ionising radiation. Reactive oxygen species can produce a variety of DNA lesions, including DNA single strand breaks con...
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