Accumulation of sumoylated Rad52 in checkpoint mutants perturbed in DNA replication |
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| Authors: | Takashi Ohuchi Masayuki Seki Kazuto Kugou Shusuke Tada Kunihiro Ohta Takemi Enomoto |
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| Institution: | 1. Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai 980-8578, Japan;2. Cellular & Molecular Biology Laboratory, RIKEN Advanced Science Institute, Hirosawa 2-1, Wako, Saitama 351-0198, Japan;3. Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba 3-8-1, Meguro-ku, Tokyo 153-8902, Japan;4. Tohoku University 21st Century COE Program “Comprehensive Research and Education Center for Planning of Drug development and Clinical Evaluation”, Sendai, Miyagi 980-8578, Japan;3. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104;4. Cell and Molecular Biology Group, Biomedical Graduate Studies, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104;5. Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104;6. Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854;1. Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain;2. CIBER Epidemiología y Salud Pública, ISCIII, Madrid, Spain;1. ENVIRON International Corporation, 1900 N. 18th Street, Suite 804, Monroe, LA 71201, United States;2. ENVIRON International Corporation, 2200 Powell Street, Suite 700, Emeryville, CA 94608, United States;3. The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709-2137, United States;4. University of New Mexico, MSC 10 5550, 1 University of New Mexico, Albuquerque, NM 87131-0001, United States |
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| Abstract: | Checkpoints are cellular surveillance and signaling pathways that regulate responses to DNA damage and perturbations of DNA replication. Here we show that high levels of sumoylated Rad52 are present in the mec1 sml1 and rad53 sml1 checkpoint mutants exposed to DNA-damaging agents such as methyl methanesulfonate (MMS) or the DNA replication inhibitor hydroxyurea (HU). The kinase-defective mutant rad53-K227A also showed high levels of Rad52 sumoylation. Elevated levels of Rad52 sumoylation occur in checkpoint mutants proceeding S phase being exposed DNA-damaging agent. Interestingly, chromatin immunoprecipitation (ChIP) on chip analyses revealed non-canonical chromosomal localization of Rad52 in the HU-treated rad53-K227A cells arrested in early S phase: Rad52 localization at dormant and early DNA replication origins. However, such unusual localization was not dependent on the sumoylation of Rad52. In addition, we also found that Rad52 could be highly sumoylated in the absence of Rad51. Double mutation of RAD51 and RAD53 exhibited the similar levels of Rad52 sumoylation to RAD53 single mutation. The significance and regulation mechanism of Rad52 sumoylation by checkpoint pathways will be discussed. |
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