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DNA Damage, Repair, and Diseases Journal of Biomedicine and Biotechnology DNA Damage, Repair, and Diseases Guest Editors: Lisa Wiesmüller, James M. Ford, and Robert H. Schiestl Journal of Biomedicine and Biotechnology DNA Damage, Repair, and Diseases Journal of Biomedicine and Biotechnology DNA Damage, Repair, and Diseases Guest Editors: Lisa Wiesmüller, James M. Ford, and Robert H. Schiestl Copyright © 2002 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in volume 2002 of “Journal of Biomedicine and Biotechnology.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Founding Managing Editor Abdelali Haoudi, Eastern Virginia Medical School, USA Editors-In-Chief H. N. Ananthaswamy, USA Marc Fellous, France Peter M. Gresshoff, Australia Advisory Board Virander Singh Chauhan, India Francis Galibert, France Pierre Tambourin, France Jean Dausset, France Jean-Claude Kaplan, France Michel Veron, France Koussay Dellagi, Tunisia Mohamed Saghi, Morocco Ahmed Farouki, Morocco Naem Shahrour, USA Associate Editors Francois Amalric, France Vladimir Larionov, USA Annie J. Sasco, France Richard Bartlett, USA David Lightfoot, USA Daniel Scherman, France Shyam K. Dube, USA Khalid Meksem, USA O. John Semmes, USA Pierre Gadal, France Allal Ouhtit, USA Pierre-Marie Sinet, France Denise M. Harmening, USA Steffen B. Petersen, Denmark Hongbin Zhang, USA Dominique Job, France Etienne Roux, France Editorial Board Kamran Abbassi, UK William N. Fishbein, USA James M. Mason, USA Khalid A. Alali, Qatar Francis Galibert, France Majid Mehtali, France Khaled Amiri, UAE Claude Gaillardin, France Emile Miginiac, France Mahmoud M. Amr, Egypt William Gelbart, USA John V. Moran, USA Claude Bagnis, France Mauro Giacca, Italy Ali Ouaissi, France Claude Balny, France Andrea J. Gonzales, USA Pamela M. Pollock, Australia Raj Bathnagar, India Marie T. Greally, Bahrain Kanury V. S. Rao, India Lynn Bird, USA Jau-Shyong Hong, USA Laure Sabatier, France Marìa A. Blasco, Spain James Huff, USA Abdelaziz Sefiani, Morocco Dominique Bonneau, France Mohamed Iqbal, Saudi Arabia James L. Sherley, USA Mohamed Boutjdir, USA Shahid Jameel, India Noel W. Solomons, Guatemala Douglas Bristol, USA Celina Janion, Poland Thomas R. Spitzer, USA Georges Calothy, France Jean-Claude Jardillier, France Michel Tibayrenc, France Ronald E. Cannon, USA Gary M. Kasof, USA M’hamed Tijane, Morocco Anne Cambon-Thomsen, France Michel Lagarde, France Christian Trepo, France Louis Dallaire, Canada Pierre Legrain, France Michel Veron, France Martine Defais, France Nan Liu, USA Jean-Michel H. Vos, USA Luiz De Marco, Brazil Yan Luo, USA LisaWiesmüller, Germany John W. Drake, USA John Macgregor, France Leila Zahed, Lebanon Hatem El Shanti, Jordan Regis Mache, France Steven L. Zeichner, USA Thomas Fanning, USA Mohamed Marrakchi, Tunisia Contents Editorial, Lisa Wiesmüller, James M. Ford, and Robert H. Schiestl Volume 2 (2002), Issue 2, Pages 45-45 Werner Syndrome, Lishan Chen and Junko Oshima Volume 2 (2002), Issue 2, Pages 46-54 Nucleotide Excision Repair, Genome Stability, and Human Disease: New Insight from Model Systems, David J. Garfinkel and Adam M. Bailis Volume 2 (2002), Issue 2, Pages 55-60 Ku and the Stability of the Genome, Anna A. Friedl Volume 2 (2002), Issue 2, Pages 61-65 Answering the Call: Coping with DNA Damage at the Most Inopportune Time, David J. Crowley and Justin Courcelle Volume 2 (2002), Issue 2, Pages 66-74 Homologous Recombination and Its Role in Carcinogenesis, Alexander J. R. Bishop and Robert H. Schiestl Volume 2 (2002), Issue 2, Pages 75-85 Recombinational DNA Repair in Cancer and Normal Cells: The Challenge of Functional Analysis, Henning Willers, Fen Xia, and Simon N. Powell Volume 2 (2002), Issue 2, Pages 86-93 Regulation of Repair by the 26S Proteasome, K. Sweder and K. Madura Volume 2 (2002), Issue 2, Pages 94-105 XRCC2 is Required for the Formation of Rad51 Foci Induced by Ionizing Radiation and DNA Cross-Linking Agent Mitomycin C, Nan Liu Volume 2 (2002), Issue 2, Pages 106-113 Journal of Biomedicine and Biotechnology • 2:2 (2002) 45–45 • PII. S1110724302001985 • http://jbb.hindawi.com EDITORIAL DNA Damage, Repair, and Diseases Lisa Wiesmuller,¨ 1 James M. Ford,2 and Robert H. Schiestl3 1University of Hamburg, Germany 2Stanford University School of Medicine , California, USA 3UCLA Schools of Medicine and Public Health, California, USA DNA is the essential carrier of genetic information in repair include many cancer susceptibility syndromes, such as all living cells. How is the huge amount of DNA in organ- Xeroderma pigmentosum, Ataxia-telangectasia, Bloom’s and isms from bacteria to humans maintained and protected Werner’s syndromes, Hereditary Non-Polyposis Colon Can- from the ravages of noxious agents in the environment? The cer, Li-Fraumeni-syndrome, and breast/ovarian cancer syn- chemical stability of the DNA molecule is not unusually drome. great, DNA undergoes several types of spontaneous modifi- The most ubiquitous and versatile modes of DNA repair cations, and it can also react with many physical and chemi- are those in which the damaged or incorrect part of a DNA cal agents, of which some are endogenous products of the cel- strand is excised and then the resulting gap is filled by re- lular metabolism (eg, reactive oxygen species) while others, pair replication using the complementary strand as template. including ionizing radiation and ultraviolet light, are threats The excision repair pathway that deals with UV-irradiation from the external environment. The resulting alterations of induced pyrimidine dimers and a large variety of cancer- DNA structure are generally incompatible with its essential causing chemical adducts to DNA is known as nucleotide role in preservation and transmission of genetic information. excision repair (NER). Several very interesting new develop- Damage to DNA can cause genetic alterations, and if genes ments in this field will be reviewed. These include DNA dam- that control cell growth are involved, these mutations can age inducible responses in both prokaryotic and eukaryotic lead to the development of cancer. Of course, DNA damage organisms, including both inducible DNA repair genes and may also result in cell death which can have serious conse- genes involved in the proteasomal/ubiquitination pathway quences for the organism of which the cell is a part; for ex- and the detection of such inducible responses using whole- ample, loss of irreplaceable neurons in the brain. Accumula- genome transcriptional profiling techniques. tion of damaged DNA has also been considered to contribute Recombination represents the irreplaceable repair mech- to some of the features of aging. It is not surprising that a anism under circumstances when DSBs appear as a result of complex set of cellular surveillance and repair mechanisms metabolic processes or genotoxic treatment. In mammalian has evolved to reverse the potentially deleterious damage that cells about half of all DSBs are repaired by homologous re- would otherwise destroy the precious blueprint for life. Some combination, half by nonhomologous end joining. The lack of these DNA repair systems are so important that life cannot of central enzyme functions can cause lethal phenotypes of be sustained without them. An increasing number of human knockout mice or result in extreme sensitivities towards ion- hereditary diseases that are characterized by severe develop- izing radiation. Moreover, correct repair of DSBs is central to mental problems and/or a predisposition to cancer have been the maintenance of genomic integrity in mammalian cells, found to be linked to deficiencies in DNA repair. since errors give rise to translocations, deletions, duplica- The many types of DNA repair include excision repair tions, expansions, and transposon integration, which accel- mechanisms targeted to the removal of bulky DNA adducts erate the multistep process of tumor progression. Therefore, and UV-induced photoproducts, base-pair alterations and recombination processes are subject to surveillance by a hier- purine loss, and DNA mismatches, and single- and double- archy of genome stabilizing factors, such as p53 and the PI3 strand DNA breaks. In addition, DNA replication, recombi- kinase ATM. nation and transcription are all involved in DNA repair path- ways. A complex interplay between intrinsic hereditary fac- Lisa Wiesmuller¨ tors and persisting DNA damage determines the susceptibil- James M. Ford ity of humans to cancer. Inherited human diseases of DNA Robert H. Schiestl © 2002 Hindawi Publishing Corporation Journal of Biomedicine and Biotechnology • 2:2 (2002) 46–54 • PII. S1110724302201011 • http://jbb.hindawi.com REVIEW ARTICLE Werner Syndrome Lishan Chen and Junko Oshima∗ Department of Pathology, Box 357470, HSB K-543, University of Washington, Seattle, WA 98195-7470, USA Received 19 December 2001; accepted 4 January 2002 Werner syndrome is a premature aging disease caused by the mutation in the WRN gene. The cloning and characterization of the WRN gene and its product allows investigators to study the disease and the human aging process at molecular level. This review summarizes the recent progresses on various aspects of the WRN research including functional analysis of the protein, interactive cloning, complexes formation, mouse models, and SNPs (single nucleotide polymorphisms). These in depth investigations have greatly advanced
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