Abstract
Mitosis is the stage of the cell cycle during which replicated chromosomes must be precisely divided to allow the formation of two daughter cells possessing equal genetic material. Much of the careful spatial and temporal organization of mitosis is maintained through post-translational modifications, such as phosphorylation and ubiquitination, of key cellular proteins. Here, we will review evidence that sumoylation, conjugation to the SUMO family of small ubiquitin-like modifiers, also serves essential regulatory roles during mitosis. We will discuss the basic biology of sumoylation, how the SUMO pathway has been implicated in particular mitotic functions, including chromosome condensation, centromere/kinetochore organization and cytokinesis, and what cellular proteins may be the targets underlying these phenomena.
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References
Andrews PD, Ovechkina Y, Morrice N, Wagenbach M, Duncan K, Wordeman L, Swedlow JR (2004) Aurora B regulates MCAK at the mitotic centromere. Dev Cell 6:253–268
Arnaoutov A, Azuma Y, Ribbeck K, Joseph J, Boyarchuk Y, Karpova T, McNally J, Dasso M (2005) Crm1 is a mitotic effector of Ran-GTP in somatic cells. Nat Cell Biol 7:626–632
Ayaydin F, Dasso M (2004) Distinct in vivo dynamics of vertebrate SUMO paralogues. Mol Biol Cell 15:5208–5218
Azuma Y, Arnaoutov A, Dasso M (2003) SUMO-2/3 regulates topoisomerase II in mitosis. J Cell Biol 163:477–487
Azuma Y, Arnaoutov A, Anan T, Dasso M (2005) PIASy mediates SUMO-2 conjugation of Topoisomerase-II on mitotic chromosomes. EMBO J 24:2172–2782
Baba D, Maita N, Jee J, Uchimura Y, Saitoh H, Sugasawa K, Hanaoka F, Tochio H, Hiroaki H, Shirakawa M (2005) Crystal structure of thymine DNA glycosylase conjugated to SUMO-1. Nature 435:979–982
Bachant J, Alcasabas A, Blat Y, Kleckner N, Elledge SJ (2002) The SUMO-1 isopeptidase Smt4 is linked to centromeric cohesion through SUMO-1 modification of DNA topoisomerase II. Mol Cell 9:1169–1182
Bachellier-Bassi S, Gadal O, Bourout G, Nehrbass U (2008) Cell cycle-dependent kinetochore localization of condensin complex in Saccharomyces cerevisiae. J Struct Biol 162:248–259
Beliakoff J, Sun Z (2006) Zimp7 and Zimp10, two novel PIAS-like proteins, function as androgen receptor coregulators. Nucl Recept Signal 4:e017
Belmont AS (2006) Mitotic chromosome structure and condensation. Curr Opin Cell Biol 18:632–638
Bharadwaj R, Qi W, Yu H (2004) Identification of two novel components of the human NDC80 kinetochore complex. J Biol Chem 279:13076–13085
Bylebyl GR, Belichenko I, Johnson ES (2003) The SUMO isopeptidase Ulp2 prevents accumulation of SUMO chains in yeast. J Biol Chem 278:44113–44120
Cheeseman IM, Desai A (2008) Molecular architecture of the kinetochore-microtubule interface. Nat Rev Mol Cell Biol 9:33–46
Cheng C, Lo Y, Liang S, Ti S, Lin F, Yeh C, Huang H, Wang T (2006) SUMO modifications control assembly of synaptonemal complex and polycomplex in meiosis of Saccharomyces cerevisiae. Genes Dev 20:2067–2081
Chung TL, Hsiao HH, Yeh YY, Shia HL, Chen YL, Liang PH, Wang AH, Khoo KH, Shoei-Lung Li S (2004) In vitro modification of human centromere protein CENP-C fragments by small ubiquitin-like modifier (SUMO) protein: definitive identification of the modification sites by tandem mass spectrometry analysis of the isopeptides. J Biol Chem 279(38):39653–39662
Cleveland DW, Mao Y, Sullivan KF (2003) Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling. Cell 112:407–421
Cooke CA, Schaar B, Yen TJ, Earnshaw WC (1997) Localization of CENP-E in the fibrous corona and outer plate of mammalian kinetochores from prometaphase through anaphase. Chromosoma 106:446–455
D’Amours D, Stegmeier F, Amon A (2004) Cdc14 and condensin control the dissolution of cohesin-independent chromosome linkages at repeated DNA. Cell 117:455–469
Dasso M (2002) The Ran GTPase: theme and variations. Curr Biol 12:R502–R508
Dasso M (2006) Ran at kinetochores. Biochem Soc Trans 34:711–715
Dasso M (2008) Emerging roles of the SUMO pathway in mitosis. Cell Div 3:5
Dawlaty MM, Malureanu L, Jeganathan KB, Kao E, Sustmann C, Tahk S, Shuai K, Grosschedl R, van Deursen JM (2008) Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha. Cell 133:103–115
Denison SH, Käfer E, May GS (1993) Mutation in the bimD gene of Aspergillus nidulans confers a conditional mitotic block and sensitivity to DNA damaging agents. Genetics 134:1085–1096
Denison C, Rudner AD, Gerber SA, Bakalarski CE, Moazed D, Gygi SP (2005) A proteomic strategy for gaining insights into protein sumoylation in yeast. Mol Cell Proteomics 4:246–254
Devoy A, Soane T, Welchman R, Mayer RJ (2005) The ubiquitin-proteasome system and cancer. Essays Biochem 41:187–203
DÃaz-MartÃnez LA, Giménez-Abián JF, Azuma Y, Guacci V, Giménez-MartÃn G, Lanier LM, Clarke DJ (2006) PIASgamma is required for faithful chromosome segregation in human cells. PLoS ONE 1:e53
Fukagawa T, Regnier V, Ikemura T (2001) Creation and characterization of temperature-sensitive CENP-C mutants in vertebrate cells. Nucleic Acids Res 29:3796–3803
Geiss-Friedlander R, Melchior F (2007) Concepts in sumoylation: a decade on. Nat Rev Mol Cell Biol 8:947–956
Glotzer M (2005) The molecular requirements for cytokinesis. Science 307:1735–1739
Haering CH, Nasmyth K (2003) Building and breaking bridges between sister chromatids. Bioessays 25:1178–1191
Hannich JT, Lewis A, Kroetz MB, Li S, Heide H, Emili A, Hochstrasser M (2005) Defining the SUMO-modified proteome by multiple approaches in Saccharomyces cerevisiae. J Biol Chem 280:4102–4110
Hauf S, Roitinger E, Koch B, Dittrich CM, Mechtler K, Peters J (2005) Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2. PLoS Biol 3:e69
Hecker C, Rabiller M, Haglund K, Bayer P, Dikic I (2006) Specification of SUMO1- and SUMO2-interacting motifs. J Biol Chem 281:16117–16127
Hirano T (2005) Condensins: organizing and segregating the genome. Curr Biol 15:R265–R275
Hirano T (2006) At the heart of the chromosome: SMC proteins in action. Nat Rev Mol Cell Biol 7:311–322
Jeong SY, Rose A, Joseph J, Dasso M, Meier I (2005) Plant-specific mitotic targeting of RanGAP requires a functional WPP domain. Plant J 42:270–282
Johnson ES (2004) Protein modification by SUMO. Annu Rev Biochem 73:355–382
Johnson ES, Blobel G (1999) Cell cycle-regulated attachment of the ubiquitin-related protein SUMO to the yeast septins. J Cell Biol 147:981–994
Joseph J, Tan S, Karpova TS, McNally JG, Dasso M (2002) SUMO-1 targets RanGAP1 to kinetochores and mitotic spindles. J Cell Biol 156:595–602
Joseph J, Liu S, Jablonski SA, Yen TJ, Dasso M (2004) The RanGAP1-RanBP2 complex is essential for microtubule-kinetochore interactions in vivo. Curr Biol 14:611–617
Kagey MH, Melhuish TA, Wotton D (2003) The polycomb protein Pc2 is a SUMO E3. Cell 113:127–137
Kapoor TM, Lampson MA, Hergert P, Cameron L, Cimini D, Salmon ED, McEwen BF, Khodjakov A (2006) Chromosomes can congress to the metaphase plate before biorientation. Science 311:388–391
Keaton MA, Lew DJ (2006) Eavesdropping on the cytoskeleton: progress and controversy in the yeast morphogenesis checkpoint. Curr Opin Microbiol 9:540–546
Kim Y, Heuser JE, Waterman CM, Cleveland DW (2008) CENP-E combines a slow, processive motor and a flexible coiled coil to produce an essential motile kinetochore tether. J Cell Biol 181:411–419
Klein UR, Haindl M, Nigg EA, Muller S (2009) RanBP2 and SENP3 function in a mitotic SUMO2/3 conjugation-deconjugation cycle on borealin. Mol Biol Cell 20:410–418
Kwon M, Hori T, Okada M, Fukagawa T (2007) CENP-C is involved in chromosome segregation, mitotic checkpoint function, and kinetochore assembly. Mol Biol Cell 18:2155–2168
Lallemand-Breitenbach V, Jeanne M, Benhenda S, Nasr R, Lei M, Peres L, Zhou J, Zhu J, Raught B, de Thé H (2008) Arsenic degrades PML or PML-RARalpha through a SUMO-triggered RNF4/ubiquitin-mediated pathway. Nat Cell Biol 10:547–555
Lan W, Zhang X, Kline-Smith SL, Rosasco SE, Barrett-Wilt GA, Shabanowitz J, Hunt DF, Walczak CE, Stukenberg PT (2004) Aurora B phosphorylates centromeric MCAK and regulates its localization and microtubule depolymerization activity. Curr Biol 14:273–286
Lee J, Kitajima TS, Tanno Y, Yoshida K, Morita T, Miyano T, Miyake M, Watanabe Y (2008) Unified mode of centromeric protection by shugoshin in mammalian oocytes and somatic cells. Nat Cell Biol 10:42–52
Lin D, Huang Y, Jeng J, Kuo H, Chang C, Chao T, Ho C, Chen Y, Lin T, Fang H, Hung C, Suen C, Hwang M, Chang K, Maul GG, Shih H (2006) Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Mol Cell 24:341–354
Mahajan R, Gerace L, Melchior F (1998) Molecular characterization of the SUMO-1 modification of RanGAP1 and its role in nuclear envelope association. J Cell Biol 140:259–270
Makhnevych T, Ptak C, Lusk CP, Aitchison JD, Wozniak RW (2007) The role of karyopherins in the regulated sumoylation of septins. J Cell Biol 177:39–49
Martin SW, Konopka JB (2004) SUMO modification of septin-interacting proteins in Candida albicans. J Biol Chem 279:40861–40867
Matsumoto T, Yanagida M (2005) The dreaPm of every chromosome: equal segregation for a healthy life of the host. Adv Exp Med Biol 570:281–310
Matunis MJ, Wu J, Blobel G (1998) SUMO-1 modification and its role in targeting the Ran GTPase-activating protein, RanGAP1, to the nuclear pore complex. J Cell Biol 140:499–509
McAinsh AD, Tytell JD, Sorger PK (2003) Structure, function, and regulation of budding yeast kinetochores. Annu Rev Cell Dev Biol 19:519–539
McEwen BF, Chan GK, Zubrowski B, Savoian MS, Sauer MT, Yen TJ (2001) CENP-E is essential for reliable bioriented spindle attachment, but chromosome alignment can be achieved via redundant mechanisms in mammalian cells. Mol Biol Cell 12:2776–2789
Meluh PB, Koshland D (1995) Evidence that the MIF2 gene of Saccharomyces cerevisiae encodes a centromere protein with homology to the mammalian centromere protein CENP-C. Mol Biol Cell 6:793–807
Meulmeester E, Kunze M, Hsiao HH, Urlaub H, Melchior F (2008) Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25. Mol Cell 30:610–619
Michaelis C, Ciosk R, Nasmyth K (1997) Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell 91:35–45
Minty A, Dumont X, Kaghad M, Caput D (2000) Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif. J Biol Chem 275:36316–36323
Montpetit B, Hazbun TR, Fields S, Hieter P (2006) Sumoylation of the budding yeast kinetochore protein Ndc10 is required for Ndc10 spindle localization and regulation of anaphase spindle elongation. J Cell Biol 174:653–663
Mukhopadhyay D, Dasso M (2007) Modification in reverse: the SUMO proteases. Trends Biochem Sci 32:286–295
Mukhopadhyay D, Ayaydin F, Kolli N, Tan S, Anan T, Kametaka A, Azuma Y, Wilkinson KD, Dasso M (2006) SUSP1 antagonizes formation of highly SUMO2/3-conjugated species. J Cell Biol 174:939–949
Musacchio A, Salmon ED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8:379–393
Palvimo JJ (2007) PIAS proteins as regulators of small ubiquitin-related modifier (SUMO) modifications and transcription. Biochem Soc Trans 35:1405–1408
Panse VG, Hardeland U, Werner T, Kuster B, Hurt E (2004) A proteome-wide approach identifies sumoylated substrate proteins in yeast. J Biol Chem 279:41346–41351
Pichler A, Gast A, Seeler JS, Dejean A, Melchior F (2002) The nucleoporin RanBP2 has SUMO1 E3 ligase activity. Cell 108:109–120
Potts PR, Yu H (2005) Human MMS21/NSE2 is a SUMO ligase required for DNA repair. Mol Cell Biol 25:7021–7032
Putkey FR, Cramer T, Morphew MK, Silk AD, Johnson RS, McIntosh JR, Cleveland DW (2002) Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E. Dev Cell 3:351–365
Reverter D, Lima CD (2005) Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex. Nature 435:687–692
Ruchaud S, Carmena M, Earnshaw WC (2007) Chromosomal passengers: conducting cell division. Nat Rev Mol Cell Biol 8:798–812
Saitoh H, Pu R, Cavenagh M, Dasso M (1997) RanBP2 associates with Ubc9p and a modified form of RanGAP1. Proc Natl Acad Sci U S A 94:3736–3741
Saitoh H, Sparrow DB, Shiomi T, Pu RT, Nishimoto T, Mohun TJ, Dasso M (1998) Ubc9p and the conjugation of SUMO-1 to RanGAP1 and RanBP2. Curr Biol 8:121–124
Sandall S, Severin F, McLeod IX, Yates JR, Oegema K, Hyman A, Desai A (2006) A Bir1-Sli15 complex connects centromeres to microtubules and is required to sense kinetochore tension. Cell 127:1179–1191
Shamu CE, Murray AW (1992) Sister chromatid separation in frog egg extracts requires DNA topoisomerase II activity during anaphase. J Cell Biol 117:921–934
Shen TH, Lin H, Scaglioni PP, Yung TM, Pandolfi PP (2006) The mechanisms of PML-nuclear body formation. Mol Cell 24:331–339
Shih H, Hales KG, Pringle JR, Peifer M (2002) Identification of septin-interacting proteins and characterization of the Smt3/SUMO-conjugation system in Drosophila. J Cell Sci 115:1259–1271
Song J, Zhang Z, Hu W, Chen Y (2005) Small ubiquitin-like modifier (SUMO) recognition of a SUMO binding motif: a reversal of the bound orientation. J Biol Chem 280:40122–40129
Stead K, Aguilar C, Hartman T, Drexel M, Meluh P, Guacci V (2003) Pds5p regulates the maintenance of sister chromatid cohesion and is sumoylated to promote the dissolution of cohesion. J Cell Biol 163:729–741
Strunnikov AV, Aravind L, Koonin EV (2001) Saccharomyces cerevisiae SMT4 encodes an evolutionarily conserved protease with a role in chromosome condensation regulation. Genetics 158:95–107
Takahashi Y, Strunnikov A (2008) In vivo modeling of polysumoylation uncovers targeting of Topoisomerase II to the nucleolus via optimal level of SUMO modification. Chromosoma 117:189–198
Takahashi Y, Yong-Gonzalez V, Kikuchi Y, Strunnikov A (2006) SIZ1/SIZ2 control of chromosome transmission fidelity is mediated by the sumoylation of topoisomerase II. Genetics 172:783–794
Takahashi Y, Dulev S, Liu X, Hiller NJ, Zhao X, Strunnikov A (2008) Cooperation of sumoylated chromosomal proteins in rDNA maintenance. PLoS Genet 4:e1000215
Tatham MH, Geoffroy M, Shen L, Plechanovova A, Hattersley N, Jaffray EG, Palvimo JJ, Hay RT (2008) RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol 10:538–546
Versele M, Thorner J (2005) Some assembly required: yeast septins provide the instruction manual. Trends Cell Biol 15:414–424
Wang X, Dai W (2005) Shugoshin, a guardian for sister chromatid segregation. Exp Cell Res 310:1–9
Wei RR, Sorger PK, Harrison SC (2005) Molecular organization of the Ndc80 complex, an essential kinetochore component. Proc Natl Acad Sci U S A 102:5363–5367
Wohlschlegel JA, Johnson ES, Reed SI, Yates JR (2004) Global analysis of protein sumoylation in Saccharomyces cerevisiae. J Biol Chem 279:45662–45668
Wong KA, Kim R, Christofk H, Gao J, Lawson G, Wu H (2004) Protein inhibitor of activated STAT Y (PIASy) and a splice variant lacking exon 6 enhance sumoylation but are not essential for embryogenesis and adult life. Mol Cell Biol 24:5577–5586
Wykoff DD, O’Shea EK (2005) Identification of sumoylated proteins by systematic immunoprecipitation of the budding yeast proteome. Mol Cell Proteomics 4:73–83
Xie Y, Kerscher O, Kroetz MB, McConchie HF, Sung P, Hochstrasser M (2007) The yeast Hex3.Slx8 heterodimer is a ubiquitin ligase stimulated by substrate sumoylation. J Biol Chem 282:34176–34184
Yen TJ, Compton DA, Wise D, Zinkowski RP, Brinkley BR, Earnshaw WC, Cleveland DW (1991) CENP-E, a novel human centromere-associated protein required for progression from metaphase to anaphase. EMBO J 10:1245–1254
Zhang X, Goeres J, Zhang H, Yen TJ, Porter ACG, Matunis MJ (2008) SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis. Mol Cell 29:729–741
Zhou W, Ryan JJ, Zhou H (2004) Global analyses of sumoylated proteins in Saccharomyces cerevisiae. Induction of protein sumoylation by cellular stresses. J Biol Chem 279:32262–32268
Zhu J, Zhu S, Guzzo CM, Ellis NA, Sung KS, Choi CY, Matunis MJ (2008) Small ubiquitin-related modifier (SUMO) binding determines substrate recognition and paralog-selective SUMO modification. J Biol Chem 283:29405–29415
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Mukhopadhyay, D., Dasso, M. (2017). The SUMO Pathway in Mitosis. In: Wilson, V. (eds) SUMO Regulation of Cellular Processes. Advances in Experimental Medicine and Biology, vol 963. Springer, Cham. https://doi.org/10.1007/978-3-319-50044-7_10
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