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Non-homologous end joining often uses microhomology: Implications for alternative end joining
Institution:1. Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, Japan;2. Leibniz Institute for Age Research—Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany;3. Howard Hughes Medical Institute, Department of Molecular Biosciences, and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA;4. Department of Neurogenomics, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan;1. Département de Médecine Nucléaire et Radiobiologie, Faculté de Médecine de des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4;2. Leonard Davis School of Gerontology of the Ethel Percy Andrus Gerontology Center, the University of Southern California, Los Angeles, CA 90089-0191, USA;3. Division of Molecular & Computational Biology, Department of Biological Sciences of the Dornsife College of Letters, Arts, and Sciences, the University of Southern California, Los Angeles, CA 90089-0191, USA;1. Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China;2. School of Life Science, Henan University, Kaifeng 475004, China;3. University of Chinese Academy of Sciences, Beijing 100049, China;4. Department of Microbiology and Li KaShing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China
Abstract:Artemis and PALF (also called APLF) appear to be among the primary nucleases involved in non-homologous end joining (NHEJ) and responsible for most nucleolytic end processing in NHEJ. About 60% of NHEJ events show an alignment of the DNA ends that use 1 or 2 bp of microhomology (MH) between the two DNA termini. Thus, MH is a common feature of NHEJ. For most naturally occurring human chromosomal deletions (e.g., after oxidative damage or radiation) and translocations, such as those seen in human neoplasms and as well as inherited chromosomal structural variations, MH usage occurs at a frequency that is typical of NHEJ, and does not suggest major involvement of alternative pathways that require more extensive MH. Though we mainly focus on human NHEJ at double-strand breaks, comparison on these points to other eukaryotes, primarily S. cerevisiae, is informative.
Keywords:Double-strand break repair  Lymphoma  Chromosomal rearrangements  V(D)J recombination  Class switch recombination
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