GPMDB0016979OtherXiao Z, et al.InstrumentNot AvailableNot availableHomo_sapiens_viruses, Human_femaleA.C.O.Vertegaal@lumc.nl25755297Leiden University Medical Center, Netherlands, et al.http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018461http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018460http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018459http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018496http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018452http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018451http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018495http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018454http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018498http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018453http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018497http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018456http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018499http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018455http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018458http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018457http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018490http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018492http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018491http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018494http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018450http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018493http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018449http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018485http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018484http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018487http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018486http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018489http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018488http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018481http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018480http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018483http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018482http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018514http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018474http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018473http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018476http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018475http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018511http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018478http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018477http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018510http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018513http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018512http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018479http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018470http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018472http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018471http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018504http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018503http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018506http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018505http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018508http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018507http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018509http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018462http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018465http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018464http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018467http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018500http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018466http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018502http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018469http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018501http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018468Not availableGPMDBGenotoxic agents can cause replication fork stalling in dividing cells because of DNA lesions, eventually leading to replication fork collapse when the damage is not repaired. Small Ubiquitin-like Modifiers (SUMOs) are known to counteract replication stress, nevertheless, only a small number of relevant SUMO target proteins are known. To address this, we have purified and identified SUMO-2 target proteins regulated by replication stress in human cells. The developed methodology enabled single step purification of His10-SUMO-2 conjugates under denaturing conditions with high yield and high purity. Following statistical analysis on five biological replicates, a total of 566 SUMO-2 targets were identified. After 2 h of hydroxyurea treatment, 10 proteins were up-regulated for SUMOylation and two proteins were down-regulated for SUMOylation, whereas after 24 h, 35 proteins were up-regulated for SUMOylation, and 13 proteins were down-regulated for SUMOylation. A site-specific approach was used to map over 1000 SUMO-2 acceptor lysines in target proteins. The methodology is generic and is widely applicable in the ubiquitin field. A large subset of these identified proteins function in one network that consists of interacting replication factors, transcriptional regulators, DNA damage response factors including MDC1, ATR-interacting protein ATRIP, the Bloom syndrome protein and the BLM-binding partner RMI1, the crossover junction endonuclease EME1, BRCA1, and CHAF1A. Furthermore, centromeric proteins and signal transducers were dynamically regulated by SUMOylation upon replication stress. Our results uncover a comprehensive network of SUMO target proteins dealing with replication damage and provide a framework for detailed understanding of the role of SUMOylation to counteract replication stress. Ultimately, our study reveals how a post-translational modification is able to orchestrate a large variety of different proteins to integrate different nuclear processes with the aim of dealing with the induced DNA damage.System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability.Xiao Zhenyu Z,Chang Jer-Gung JG,Hendriks Ivo A IA,Sigurðsson Jón Otti JO,Olsen Jesper V JV,Vertegaal Alfred C O AC,Xiao Zhenyu Z, Chang Jer-Gung JG, Hendriks Ivo A IA, Sigurðsson Jón Otti JO, Olsen Jesper V JV, Vertegaal Alfred C O ACreactivity, sumoylation, anatomical systems, wide/broad, determination, SUMO-Conjugations, SUMO-protein conjugation, Proteins, Gene, proteins, protein sumolation, whole genome, broad, body system, organ system, SUMO Conjugation, Protein Gene Products, Gene Proteins, polypeptide, SUMO, wide, Sumoylations, responsivity, chemical analysis, Protein, Gene Products, system, assay, SUMO-Conjugation, response, connected anatomical system, small ubiquitin-related protein 1 conjugation, Genomes.data, human being, Smt3b, Proteins, Smt3h2, Gene, Homo sapiense, Sentrin-2, HSMT3, Cell, polypeptide, Homo spaiens, Homo sapien, Homo sapian, Homo sapians, Protein, 3.1.3.48, Gene Products, techniques, Homo sapeins, SMT3 homolog 2, SMT3 homolog 1, Homo sapients, Step, PTPSTEP, Humo sapiens, proteins, Striatum-enriched protein-tyrosine phosphatase, SUMO-3., Ubiquitin-like protein SMT3B, procedures, man, Homo sapines, SUMO-2, human, SUMO-3, Protein Gene Products, Gene Proteins, Homo spiens, "human" EXACT genbank_common_name [], Neural-specific protein-tyrosine phosphatase, Ubiquitin-like protein SMT3A, Homo sapience, STEP, Smt3A, Homo sampiens, Smt3B, Home sapiens, methodologysmall, sumoylation, wide/broad, determination, SUMO-Conjugations, SUMO-protein conjugation, Proteins, Gene, ATP Dependent Proteolysis Factor 1, broad, Ubiquitin carboxyl extension protein 80, CEP52, body system, Human, polypeptide, Ubiquitin A-52 residue ribosomal protein fusion product 1, reduced, Ubiquitin-related 2, Sumoylations, responsivity, chemical analysis, Protein, Gene Products, system, HMG-20, tiny, connected anatomical system, ubiquitin-like protein modifier, ATP-Dependent Proteolysis Factor 1, small ubiquitin-related protein 1 conjugation, Genomes., Ubiquitin, reactivity, covalent modifier, anatomical systems, High Mobility Protein 20, underdeveloped, hypoplasia, Human Ubiquitin, Ubiquitin-related 1, proteins, protein sumolation, whole genome, organ system, SUMO Conjugation, Protein Gene Products, APF-1, Gene Proteins, 40S ribosomal protein S27a, wide, 60S ribosomal protein L40, ubiquitin, Ubiquitin-related, assay, SUMO-Conjugation, response, protein tagging activityprojections, posttranslational modification, Hydroxycarbamid, HSN1E, SUMO-protein conjugation, SCKL1, CAF1B, Homo sapiense, P150, PPP1R53, Damage, FCTCS, MAGE-E1 antigen, Damages, rat, Readability, Homo sapien, Roles, Homo sapians, Sumoylations, Urea, IRIS, Concepts, 2, 3, BROVCA1, DNA., small ubiquitin-related protein 1 conjugation, treatment, rabGAPLP, thymus nucleic acid, posttranslational amino acid modification, Homo sapients, High Mobility Protein 20, BRCC1, AL024058, activation inducer molecule, developmental field, PTPSTEP, BS, hypoplasia, Bloom syndrome protein, PNCA4, Ubiquitin-related 1, N-hydroxyurea, RabGAP-5, proteins, procedures, protein sumolation, number of, SUMO-2, SUMO-3, mus309 protein, APF-1, Homo sapience, HCA1, hydrea, RUSC3, papilla, Role Concepts, disease management, Double-Stranded DNA, N-carbamoylhydroxylamine, deoxyribonucleic acids, C87205, DNAn, GAPO, Home sapiens, BLAP75, Bloom syndrome homolog (human) protein, ATR, junction, CAF-1, anatomical protrusion, mouse, lamina, BRCAI, flanges, extra or missing physical or functional parts, future organ, Double-Stranded, response to DNA damage stimulus, CEP52, HSMT3, 2H2, results, (Deoxyribonucleotide)n+m, Role Concept, replication focus, carbamohydroximic acid, Homo sapian, DAMAGE, Hepatocellular carcinoma-associated protein 1, 3.1.3.48, shelf, Role, carbamoyl oxime, BLM protein, desoxyribose nucleic acid, SMT3 homolog 2, SMT3 homolog 1, Ubiquitin, DNA Injury, early T-cell activation antigen p60, RUTBC3, ADCADN, DNA Injuries, 4932432N11Rik, PTM, Step, shelves, oxyurea, RECQL3, Human Ubiquitin, expanded, RECQ2, Striatum-enriched protein-tyrosine phosphatase, Ubiquitin-like protein SMT3B, InChI=1/CH4N2O2/c2-1(4)3-5/h5H, Homo sapines, projection, ridge, human, RECQL2, RABGAP5, Genotoxic, Ubiquitin-like protein SMT3A, enlarged, STEP, MMS4L, spine, post-translational modification, carbamyl hydroxamate, ds DNA, 8430415E05Rik, DNA, mMage-e1, CD69, carbamohydroxamic acid, RNF53, big, sumoylation, human being, DNS, Genotoxic Stresses, (Deoxyribonucleotide)n, SUMO-Conjugations, lamellae, replication fork stalling, number, (H3, Gene, Smt3h2, EA1, ATP Dependent Proteolysis Factor 1, Ubiquitin carboxyl extension protein 80, Cac1p, MLR-3, Sentrin-2, NC(=O)NO, DNA Damages, SLX2A, NFBD1, process of organ, Deoxyribonucleic acids, 4)/f/h3H, Human, protrusion, Stresses, lamella, Homo spaiens, organ field, large, bloom helicase, AIM, hydroxycarbamide, Deoxyribonucleic Acid, reduced, InChIKey=VSNHCAURESNICA-DTXNPOPMCG, Nfbd1, Gene Products, HMG-20, field, tiny, ubiquitin-like protein modifier, hydroxy-, early activation antigen CD69, MAP, BLM, study, Injury, cellular DNA damage response, CH4N2O2, ligand, Transducer, mKIAA0170, Double Stranded, ridges, AI847422, posttranslational protein modification, FANCS, man, response to genotoxic stress, 40S ribosomal protein S27a, Hydroxyharnstoff, leukocyte surface antigen Leu-23, Neural-specific protein-tyrosine phosphatase, negative regulation of DNA replication at replication fork barrier, Blm protein, AL023013, Homo sampiens, great, ubiquitin, has or lacks parts of type, C-type lectin domain family 2 member C, (Deoxyribonucleotide)m, cob, protein tagging activity, laminae, statistical analysis, AA413496, small, DNA damage response, MUTYH-Associated Polyposis, FRP1, Smt3b, DNAn+1, anatomical process, Alpha-dystrobrevin-associated MAGE Protein, Proteins, DNMT, PSCP, CAF1, function, SCKL, MCMT, TEM8, Cell, Concept, mereological quality, polypeptide, 6820401C03, BL-AC/P26, replication fork blocking, SUMO, Ubiquitin A-52 residue ribosomal protein fusion product 1, anatomical junction, Ubiquitin-related 2, FAAP75, Protein, 1700034M03Rik, techniques, ds-DNA, ATP-Dependent Proteolysis Factor 1, Homo sapeins, C79893, C9orf76, flange, Drosophila melanogaster, organ process, CXXC9, covalent modifier, MEC1, Genotoxic Stress, underdeveloped, RGD1560259, Humo sapiens, deoxyribonucleic acid, mKIAA1861, Understanding, MYH-Associated Polyposis, cblB, CFAP23, post-translational amino acid modification, Injuries, Protein Gene Products, SUMO Conjugation, Gene Proteins, process, processes, Homo spiens, "human" EXACT genbank_common_name [], 60S ribosomal protein L40, GP32/28, CAF1P150, Smt3A, Smt3B, cardinality, Hydrea, Stress, Oncocarbide, Desoxyribonukleinsaeure, processus, Ubiquitin-related, SUMO-Conjugation, CLEC2C, methodology160979http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018476dbgap_ncbi~0patentfamilies~0rfam~0merops~0complex-portal~0pdbekb~194wormbaseparasite~0embl-covid19~0reactome~0emdb~0wgs_masters~0ebiweb_resources~0opentargets_genetics~0biomodels_all~0ipd-mhc~0ebiweb_teams~0taxonomy~0genome_assembly~0sc-experiments~0ebiweb_people~0enzymeportal_enzymes~0ipd-nhkir~0cellosaurus~0pdbe~0chebi~0patentproteins~0uniref~0chembl~0interpro7~6gpcrdb~0hgnc~0sc-genes~0intact~0rhea~0ebiweb_training~0alphafold~0imgt-hla~0patentnucleotides~0ensemblroot~0eva_studies~0non-coding~0europepmc~0pubmed~1identifiers_registry~0pdbechem~0hpa-covid19~0eva-variants-covid19~0biosamples~0gwas_catalog~0biotools~0tls_masters~0mesh~0uniprot~774coding~0sra~0opentargets~0efo~0embl-pathogen~0project~0pride~1human_diseases~0geo_datasets~0embl~0treefam~0uniparc~0ols~0dgva~0intenz~0go~0tsa_masters~0biosamples-covid19~0ebiweb_corporate~0omim~0lrg~0earlycause-molecular-sequences~0ipd-kir~0empiar~0rnacentral~0orcid_data_claims~0gpmdb~2lineage-covid19~0metagenomics~0pfam~0pride archive~1varsite~00Resource Reanalysis0.00.00.0049352251696483651.00.0falseSystem-wide analysis of SUMOylation dynamics in response to replication stress reveals novel SUMO target proteins and acceptor lysines relevant for genome stability.Data from ProteomeXchange, PXD ID: PXD001736. File: 20140408_QE_UP_U2OS1222_2h_04a.mzml. Published as part of . From the Abstract: {{i}} To address this, we have purified and identified SUMO-2 target proteins regulated by replication stress in human cells. The developed methodology enabled single step purification of His10-SUMO-2 conjugates under denaturing conditions with high yield and high purity ... {{/i}}2015-03-14GPM3231001847625755297PXD001736PXD001736