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The frequency of poly(G) tracts in the human genome and their use as a sensor of DNA damage
Institution:1. Departamento de Biologia Geral, Universidade Federal de Viçosa, 36570-000, Viçosa, MG, Brazil;2. Departamento de Biologia Vegetal, Universidade Federal de Viçosa, 36570-000, Viçosa, MG, Brazil;3. Departamento de Entomologia, Universidade Federal de Viçosa, 36570-000, Viçosa, MG, Brazil;4. Laboratório de Ecologia, Departamento de Biologia Geral, Universidade Federal de Viçosa, Av. Peter Henry Rolfs s/n, 36570-000, Viçosa, MG, Brazil;1. Department of Global Health, College of Public Health, University of South Florida, Tampa, FL 33612, USA;2. Department of Biological Sciences, 100 Green Street, Ford Hall, Smith College, Northampton, MA 01063, USA;3. Genome Biology Division, Molecular Parasitology Group, New England Biolabs, 240 County Road, Ipswich, MA 01938, USA;4. Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, 501 D. W. Brooks Drive, Athens, GA 30602, USA;3. Department of Medical Neurobiology, Institute for Medical Research Israel-Canada (IMRIC) and the Edmond and Lily Safra Center for Brain Sciences (ELSC), Faculty of Medicine, Hebrew University, Jerusalem 91120, Israel;4. Department of Biosensorics, Institute of Physiology, University of Hohenheim, 70599 Stuttgart, Germany;1. The Institutes of Brain Science, The State Key Laboratory of Medical Neurobiology, and The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China;2. Molecular and Cellular Neuroscience Department, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA;1. Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy;2. I.R.C.C.S. Neuromed, Pozzilli IS, Italy;3. Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy;4. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy;5. U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genoa, Italy
Abstract:Tandem repeats of short DNA sequences are commonly found in human DNA. These simple sequence repeats or microsatellites are highly polymorphic in the human genome. Since the anti-tumour agent cisplatin preferentially forms DNA adducts at runs of consecutive guanine nucleotides (poly(G)), the position and frequency of occurrence of poly(G) sequences in the updated human genome was investigated. There are more runs of consecutive guanines than would be expected by random chance. This especially true for poly(G) sequences longer than approximately n = 9. A plot of poly(G) length against log(observed/expected) frequency produced a straight line for n > 9. A similar observation was also found for poly(A) DNA sequence repeats. This data implied that the increase in observed/expected frequency is directly related to length of DNA repeat. It was proposed that long runs of consecutive guanine nucleotides could be a sensitive sensor of cellular DNA damage since a number of DNA damaging agents cause lesions at poly(G) sequences.
Keywords:Cisplatin  DNA damage sensor  Exponential increase  Poly(G)  Poly(A)
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