Mec1-dependent phosphorylation of Mms21 modulates its SUMO ligase activity |
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| Affiliation: | 1. School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA;2. Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA;1. School of Biological and Biomedical Sciences, South Road, Durham University, Durham DH1 3LE, UK;2. Department of Life Sciences, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy;3. Fondazione Filarete, Viale Ortles 22/4, 20139 Milan, Italy;4. Plant Sciences Division, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK;5. Rothamsted Research, West Common, Harpenden, Hertfordshire AL5 2JQ, UK;6. School of Life Sciences University of Warwick, Gibbet Hill Road, Coventry CV4 7ES, UK;1. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK;2. Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK;1. Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands;2. Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU, Oxford, United Kingdom;3. Division of Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands;4. Department of Genetics, Cancer Genomics Netherlands, and Department of Radiation Oncology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands;1. Department of Diagnostic Imaging, USA;2. Warren Alpert Medical School of Brown University, USA;3. Lifespan Biostatistics Core, USA;4. Department of Medical Physics, USA;5. Rhode Island Hospital, USA |
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| Abstract: | The SUMO ligase Mms21, which is a subunit of the Smc5/6 complex, is required for DNA repair. Here we present results showing that Mms21 was phosophorylated during S-phase in a manner dependent on the DNA damage kinase Mec1. Phosphorylation of Mms21 occurred in unchallenged cells, but was more abundant in the presence of DNA damaging agents. Mass spectrometry identified five phosphorylated serines organized in two regions of Mms21, and two C-terminal serines, S260 and S261, formed part of a Mec1/Tel1 consensus motif. Nonphosphorylatable substitutions of the C-terminal serines, inactivation of Mec1 or removal of the Mms21 C-terminus all abolished Mms21 phosphorylation. Additionally, strains carrying Mms21 phosphoablative alleles displayed reduced SUMO ligase activity, sensitivity to MMS and an increased rate of chromosome loss in the presence of MMS. We propose that one function of S260 S261 phosphorylation is to positively regulate the SUMO ligase activity of Mms21 and thereby promote genomic stability. |
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| Keywords: | Mms21 SUMOylation Smc5/6 Phosphorylation Mec1 |
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