The sliding clamp protein PCNA, Aurora-A, Aurora-B, Borealin, and various topoisomerases can be SUMOylated (reviewed in Wan et al. 2012). SUMOylation of PCNA appears to reduce formation of double-strand breaks and inappropriate recombination (reviewed in Watts 2006, Watts 2007, Dieckman et al. 2012, Gazy and Kupiec 2012). SUMOylation of Aurora-A, Aurora-B, and Borealin is necessary for proper chromosome segregation. SUMOylation of topoisomerases is observed in response to damage caused by inhibitors of topoisomerases.
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Hendriks IA, D'Souza RC, Yang B, Verlaan-de Vries M, Mann M, Vertegaal AC.; ''Uncovering global SUMOylation signaling networks in a site-specific manner.''; PubMedEurope PMCScholia
Mo YY, Yu Y, Shen Z, Beck WT.; ''Nucleolar delocalization of human topoisomerase I in response to topotecan correlates with sumoylation of the protein.''; PubMedEurope PMCScholia
Ori A, Banterle N, Iskar M, Iskar M, Andrés-Pons A, Escher C, Khanh Bui H, Sparks L, Solis-Mezarino V, Rinner O, Bork P, Lemke EA, Beck M.; ''Cell type-specific nuclear pores: a case in point for context-dependent stoichiometry of molecular machines.''; PubMedEurope PMCScholia
Suntharalingam M, Wente SR.; ''Peering through the pore: nuclear pore complex structure, assembly, and function.''; PubMedEurope PMCScholia
Ban R, Nishida T, Urano T.; ''Mitotic kinase Aurora-B is regulated by SUMO-2/3 conjugation/deconjugation during mitosis.''; PubMedEurope PMCScholia
Watts FZ.; ''Sumoylation of PCNA: Wrestling with recombination at stalled replication forks.''; PubMedEurope PMCScholia
Rabut G, Doye V, Ellenberg J.; ''Mapping the dynamic organization of the nuclear pore complex inside single living cells.''; PubMedEurope PMCScholia
Hsiao HH, Meulmeester E, Frank BT, Melchior F, Urlaub H.; ''"ChopNSpice," a mass spectrometric approach that allows identification of endogenous small ubiquitin-like modifier-conjugated peptides.''; PubMedEurope PMCScholia
Fontoura BM, Blobel G, Matunis MJ.; ''A conserved biogenesis pathway for nucleoporins: proteolytic processing of a 186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96.''; PubMedEurope PMCScholia
Agostinho M, Santos V, Ferreira F, Costa R, Cardoso J, Pinheiro I, Rino J, Jaffray E, Hay RT, Ferreira J.; ''Conjugation of human topoisomerase 2 alpha with small ubiquitin-like modifiers 2/3 in response to topoisomerase inhibitors: cell cycle stage and chromosome domain specificity.''; PubMedEurope PMCScholia
Isik S, Sano K, Tsutsui K, Seki M, Enomoto T, Saitoh H, Tsutsui K.; ''The SUMO pathway is required for selective degradation of DNA topoisomerase IIbeta induced by a catalytic inhibitor ICRF-193(1).''; PubMedEurope PMCScholia
Díaz-Martínez LA, Giménez-Abián JF, Azuma Y, Guacci V, Giménez-Martín G, Lanier LM, Clarke DJ.; ''PIASgamma is required for faithful chromosome segregation in human cells.''; PubMedEurope PMCScholia
Mao Y, Desai SD, Liu LF.; ''SUMO-1 conjugation to human DNA topoisomerase II isozymes.''; PubMedEurope PMCScholia
Lin DH, Stuwe T, Schilbach S, Rundlet EJ, Perriches T, Mobbs G, Fan Y, Thierbach K, Huber FM, Collins LN, Davenport AM, Jeon YE, Hoelz A.; ''Architecture of the symmetric core of the nuclear pore.''; PubMedEurope PMCScholia
Kamitani T, Kito K, Nguyen HP, Fukuda-Kamitani T, Yeh ET.; ''Characterization of a second member of the sentrin family of ubiquitin-like proteins.''; PubMedEurope PMCScholia
Cronshaw JM, Krutchinsky AN, Zhang W, Chait BT, Matunis MJ.; ''Proteomic analysis of the mammalian nuclear pore complex.''; PubMedEurope PMCScholia
Gali H, Juhasz S, Morocz M, Hajdu I, Fatyol K, Szukacsov V, Burkovics P, Haracska L.; ''Role of SUMO modification of human PCNA at stalled replication fork.''; PubMedEurope PMCScholia
Impens F, Radoshevich L, Cossart P, Ribet D.; ''Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli.''; PubMedEurope PMCScholia
Matafora V, D'Amato A, Mori S, Blasi F, Bachi A.; ''Proteomics analysis of nucleolar SUMO-1 target proteins upon proteasome inhibition.''; PubMedEurope PMCScholia
Gazy I, Kupiec M.; ''The importance of being modified: PCNA modification and DNA damage response.''; PubMedEurope PMCScholia
Freudenthal BD, Brogie JE, Gakhar L, Kondratick CM, Washington MT.; ''Crystal structure of SUMO-modified proliferating cell nuclear antigen.''; PubMedEurope PMCScholia
Kabachinski G, Schwartz TU.; ''The nuclear pore complex--structure and function at a glance.''; PubMedEurope PMCScholia
Rallabhandi P, Hashimoto K, Mo YY, Beck WT, Moitra PK, D'Arpa P.; ''Sumoylation of topoisomerase I is involved in its partitioning between nucleoli and nucleoplasm and its clearing from nucleoli in response to camptothecin.''; PubMedEurope PMCScholia
Werner A, Flotho A, Melchior F.; ''The RanBP2/RanGAP1*SUMO1/Ubc9 complex is a multisubunit SUMO E3 ligase.''; PubMedEurope PMCScholia
Bernier-Villamor V, Sampson DA, Matunis MJ, Lima CD.; ''Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1.''; PubMedEurope PMCScholia
Klein UR, Haindl M, Nigg EA, Muller S.; ''RanBP2 and SENP3 function in a mitotic SUMO2/3 conjugation-deconjugation cycle on Borealin.''; PubMedEurope PMCScholia
Wan J, Subramonian D, Zhang XD.; ''SUMOylation in control of accurate chromosome segregation during mitosis.''; PubMedEurope PMCScholia
Mao Y, Sun M, Desai SD, Liu LF.; ''SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage.''; PubMedEurope PMCScholia
Pfander B, Moldovan GL, Sacher M, Hoege C, Jentsch S.; ''SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase.''; PubMedEurope PMCScholia
Dieckman LM, Freudenthal BD, Washington MT.; ''PCNA structure and function: insights from structures of PCNA complexes and post-translationally modified PCNA.''; PubMedEurope PMCScholia
Su HL, Li SS.; ''Molecular features of human ubiquitin-like SUMO genes and their encoded proteins.''; PubMedEurope PMCScholia
Dawlaty MM, Malureanu L, Jeganathan KB, Kao E, Sustmann C, Tahk S, Shuai K, Grosschedl R, van Deursen JM.; ''Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha.''; PubMedEurope PMCScholia
Tammsalu T, Matic I, Jaffray EG, Ibrahim AFM, Tatham MH, Hay RT.; ''Proteome-wide identification of SUMO2 modification sites.''; PubMedEurope PMCScholia
Kosinski J, Mosalaganti S, von Appen A, Teimer R, DiGuilio AL, Wan W, Bui KH, Hagen WJ, Briggs JA, Glavy JS, Hurt E, Beck M.; ''Molecular architecture of the inner ring scaffold of the human nuclear pore complex.''; PubMedEurope PMCScholia
Papouli E, Chen S, Davies AA, Huttner D, Krejci L, Sung P, Ulrich HD.; ''Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p.''; PubMedEurope PMCScholia
Fernández-Miranda G, Pérez de Castro I, Carmena M, Aguirre-Portolés C, Ruchaud S, Fant X, Montoya G, Earnshaw WC, Malumbres M.; ''SUMOylation modulates the function of Aurora-B kinase.''; PubMedEurope PMCScholia
PCNA is SUMOylated with SUMO1 at lysine-164, lysine-254, and other residues (Papouli et al. 2005, Pfander et al. 2005, Gali et al. 2012, Impens et al. 2014). SUMO1 is predominant in vivo. SUMOylation prevents double strand break formation and recombination if DNA replication stalls at lesions (Gali et al. 2012). This is comparable to the situation in Saccharomyces cerevisiae where sumoylated PCNA recruits the Srs2 helicase to prevent recombination during S phase (Pfander et al. 2005, Papouli et al. 2005). In the yeast PCNA homolog, SUMO at lysine-164 is located on the opposite face of PCNA from the face that interacts with DNA polymerase (Freudenthal et al. 2011).
TOP2A is SUMOylated with SUMO1 (Mao et al. 2000, Dawlaty et al. 2008, Matafora et al. 2009, Impens et al. 2014). SUMOylation is observed in response to TOP2A-mediated DNA damage induced by teniposide.
TOP2B is SUMOylated with SUMO1 (Mao et al. 2000, Isik et al. 2003). SUMOylation is observed in response to topoisomerase-mediated DNA damage induced by teniposide.
PIAS4 SUMOylates TOP2A with SUMO2,3 (Diaz-Martinez et al. 2006, Agostinho et al. 2008, Impens et al. 2014, Tammsalu et al. 2014). SUMOylation is observed in interphase and mitosis in response to inhibitors of topoisomerase. SUMOylated TOP2A is localized to centromeres during mitosis.
TOP1 is SUMOylated at lysine-117 with SUMO1 (Mao et al. 2000, Mo et al. 2002, Rallabhandi et al. 2002, Impens et al. 2014). SUMOylation is observed in response to the topoisomerase inhibitor camptothecin and causes nucleolar delocalization of TOP1.
During early mitosis (before metaphase) RANBP2 in the RANBP2:RANGAP-SUMO:UBC9 complex SUMOylates CDCA8 (Borealin) with SUMO2,3 at unknown lysine residues (Klein et al. 2009, Fernandez-Miranda et al. 2010, Ban et al. 2011, Werner et al. 2012, Hendriks et al. 2014). CDCA8 can also be SUMOylated with SUMO1 but SUMO2,3 is observed to predominate in vivo. At this time PIAS3 also SUMOylates AURKB (Aurora-B) at lysine-202 with SUMO2,3. The SUMOylated complex is observed in the cytosol after the nuclear envelope has broken down. As inferred from mouse, failure to SUMOylate AURKB causes defective centromeric function and abnormal chromosome segregation (Fernandez-Miranda et al. 2010).
As inferred from mouse homologs, AURKA (Aurora-A) is SUMOylated at lysine-258 with SUMO1. AURKA, SUMO1, and UBE2I (UBC9) colocalize to centrisomes and the mitotic spindle. SUMOylation of AURKA is required for proper localization to the microtubules of the mitotic spindle therefore SUMOylated AURKA is assumed to be located on spindles in the cytosol during metphase.
RANBP2 of the nuclear pore complex SUMOylates TOP2A with SUMO1 (Dawlaty et al. 2008, Impens et al. 2014). SUMOylated TOP2A is localized to centromeres. As inferred from mouse homologs, SUMOylation of TOP2A by RANBP2 is required for resolution of sister centromeres (Dawlaty et al. 2008).
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