Role of yeast Rad5 and its human orthologs,HLTF and SHPRH in DNA damage tolerance |
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| Authors: | Ildiko Unk Ildikó Hajdú András Blastyák Lajos Haracska |
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| Institution: | 1. College of Life Sciences, Capital Normal University, Beijing 100048, China;2. Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada;3. From the School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8002, Japan;4. the Graduate School of Medical Life Sciences, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan;5. the Sanford-Burnham Medical Research Institute, La Jolla, California 92037;6. the Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;1. Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA;2. Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA;3. Departament de Física Fonamental, Facultat de Física, Universitat de Barcelona, Barcelona 08028, Spain;4. CIBER-BBN de Bioingenieria, Biomateriales y Nanomedicina, Instituto de Sanidad Carlos III, Madrid 28029, Spain;1. Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA |
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| Abstract: | In the yeast Saccharomyces cerevisiae, the Rad6–Rad18 DNA damage tolerance pathway constitutes a major defense system against replication fork blocking DNA lesions. The Rad6–Rad18 ubiquitin-conjugating/ligase complex governs error-free and error-prone translesion synthesis by specialized DNA polymerases, as well as an error-free Rad5-dependent postreplicative repair pathway. For facilitating replication through DNA lesions, translesion synthesis polymerases copy directly from the damaged template, while the Rad5-dependent damage tolerance pathway obtains information from the newly synthesized strand of the undamaged sister duplex. Although genetic data demonstrate the importance of the Rad5-dependent pathway in tolerating DNA damages, there has been little understanding of its mechanism. Also, the conservation of the yeast Rad5-dependent pathway in higher order eukaryotic cells remained uncertain for a long time. Here we summarize findings published in recent years regarding the role of Rad5 in promoting error-free replication of damaged DNA, and we also discuss results obtained with its human orthologs, HLTF and SHPRH. |
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