The Smc complexes in DNA damage response

Cell & Bioscience

Hongtao Yu¹  Nan Wu¹ 

[1] Department of Pharmacology, Howard Hughes Medical Institute, 6001 Forest Park Road, Dallas, TX 75390, USA

关键词: SUMO;    rDNA;    DNA damage checkpoint;    DNA repair;    homologous recombination;    Smc6;    Smc5;    Condensin;    Cohesin;   

Others  :  793642
DOI  :  10.1186/2045-3701-2-5

 received in 2011-12-07, accepted in 2012-02-27,  发布年份 2012

【 摘 要 】

The structural maintenance of chromosomes (Smc) proteins regulate nearly all aspects of chromosome biology and are critical for genomic stability. In eukaryotes, six Smc proteins form three heterodimers--Smc1/3, Smc2/4, and Smc5/6--which together with non-Smc proteins form cohesin, condensin, and the Smc5/6 complex, respectively. Cohesin is required for proper chromosome segregation. It establishes and maintains sister-chromatid cohesion until all sister chromatids achieve bipolar attachment to the mitotic spindle. Condensin mediates chromosome condensation during mitosis. The Smc5/6 complex has multiple roles in DNA repair. In addition to their major functions in chromosome cohesion and condensation, cohesin and condensin also participate in the cellular DNA damage response. Here we review recent progress on the functions of all three Smc complexes in DNA repair and their cell cycle regulation by posttranslational modifications, such as acetylation, phosphorylation, and sumoylation. An in-depth understanding of the mechanisms by which these complexes promote DNA repair and genomic stability may help us to uncover the molecular basis of genomic instability in human cancers and devise ways that exploit this instability to treat cancers.

【 授权许可】

   
2012 Wu and Yu; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Losada A, Hirano T: Dynamic molecular linkers of the genome: the first decade of SMC proteins. Genes Dev 2005, 19:1269-1287.
• [2]Nasmyth K: Segregating sister genomes: the molecular biology of chromosome separation. Science 2002, 297:559-565.
• [3]Hirano T: Condensins: organizing and segregating the genome. Curr Biol 2005, 15:R265-275.
• [4]Potts PR: The Yin and Yang of the MMS21-SMC5/6 SUMO ligase complex in homologous recombination. DNA Repair (Amst) 2009, 8:499-506.
• [5]Lehmann AR: The role of SMC proteins in the responses to DNA damage. DNA Repair (Amst) 2005, 4:309-314.
• [6]Hirano T: At the heart of the chromosome: SMC proteins in action. Nat Rev Mol Cell Biol 2006, 7:311-322.
• [7]Nasmyth K, Haering CH: The structure and function of SMC and kleisin complexes. Annu Rev Biochem 2005, 74:595-648.
• [8]Melby TE, Ciampaglio CN, Briscoe G, Erickson HP: The symmetrical structure of structural maintenance of chromosomes (SMC) and MukB proteins: long, antiparallel coiled coils, folded at a flexible hinge. J Cell Biol 1998, 142:1595-1604.
• [9]Anderson DE, Losada A, Erickson HP, Hirano T: Condensin and cohesin display different arm conformations with characteristic hinge angles. J Cell Biol 2002, 156:419-424.
• [10]Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S: Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 2004, 73:39-85.
• [11]Stracker TH, Petrini JH: The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol 2011, 12:90-103.
• [12]Onn I, Heidinger-Pauli JM, Guacci V, Unal E, Koshland DE: Sister chromatid cohesion: a simple concept with a complex reality. Annu Rev Cell Dev Biol 2008, 24:105-129.
• [13]Unal E, Heidinger-Pauli JM, Kim W, Guacci V, Onn I, Gygi SP, Koshland DE: A molecular determinant for the establishment of sister chromatid cohesion. Science 2008, 321:566-569.
• [14]Rolef Ben-Shahar T, Heeger S, Lehane C, East P, Flynn H, Skehel M, Uhlmann F: Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion. Science 2008, 321:563-566.
• [15]Zhang J, Shi X, Li Y, Kim BJ, Jia J, Huang Z, Yang T, Fu X, Jung SY, Wang Y, et al.: Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast. Mol Cell 2008, 31:143-151.
• [16]Rowland BD, Roig MB, Nishino T, Kurze A, Uluocak P, Mishra A, Beckouet F, Underwood P, Metson J, Imre R, et al.: Building sister chromatid cohesion: smc3 acetylation counteracts an antiestablishment activity. Mol Cell 2009, 33:763-774.
• [17]Nishiyama T, Ladurner R, Schmitz J, Kreidl E, Schleiffer A, Bhaskara V, Bando M, Shirahige K, Hyman AA, Mechtler K, et al.: Sororin mediates sister chromatid cohesion by antagonizing Wapl. Cell 2010, 143:737-749.
• [18]Rankin S, Ayad NG, Kirschner MW: Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates. Mol Cell 2005, 18:185-200.
• [19]Schmitz J, Watrin E, Lenart P, Mechtler K, Peters JM: Sororin is required for stable binding of cohesin to chromatin and for sister chromatid cohesion in interphase. Curr Biol 2007, 17:630-636.
• [20]Gandhi R, Gillespie PJ, Hirano T: Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase. Curr Biol 2006, 16:2406-2417.
• [21]Kueng S, Hegemann B, Peters BH, Lipp JJ, Schleiffer A, Mechtler K, Peters JM: Wapl controls the dynamic association of cohesin with chromatin. Cell 2006, 127:955-967.
• [22]Hauf S, Roitinger E, Koch B, Dittrich CM, Mechtler K, Peters JM: Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2. PLoS Biol 2005, 3:e69.
• [23]Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y: Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 2006, 441:46-52.
• [24]Riedel CG, Katis VL, Katou Y, Mori S, Itoh T, Helmhart W, Galova M, Petronczki M, Gregan J, Cetin B, et al.: Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I. Nature 2006, 441:53-61.
• [25]Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H: PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell 2006, 10:575-585.
• [26]Uhlmann F, Wernic D, Poupart MA, Koonin EV, Nasmyth K: Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast. Cell 2000, 103:375-386.
• [27]Phipps J, Nasim A, Miller DR: Recovery, repair, and mutagenesis in Schizosaccharomyces pombe. Adv Genet 1985, 23:1-72.
• [28]Birkenbihl RP, Subramani S: Cloning and characterization of rad21 an essential gene of Schizosaccharomyces pombe involved in DNA double-strand-break repair. Nucleic Acids Res 1992, 20:6605-6611.
• [29]Sjogren C, Nasmyth K: Sister chromatid cohesion is required for postreplicative double-strand break repair in Saccharomyces cerevisiae. Curr Biol 2001, 11:991-995.
• [30]Sonoda E, Matsusaka T, Morrison C, Vagnarelli P, Hoshi O, Ushiki T, Nojima K, Fukagawa T, Waizenegger IC, Peters JM, et al.: Scc1/Rad21/Mcd1 is required for sister chromatid cohesion and kinetochore function in vertebrate cells. Dev Cell 2001, 1:759-770.
• [31]Schar P, Fasi M, Jessberger R: SMC1 coordinates DNA double-strand break repair pathways. Nucleic Acids Res 2004, 32:3921-3929.
• [32]Atienza JM, Roth RB, Rosette C, Smylie KJ, Kammerer S, Rehbock J, Ekblom J, Denissenko MF: Suppression of RAD21 gene expression decreases cell growth and enhances cytotoxicity of etoposide and bleomycin in human breast cancer cells. Mol Cancer Ther 2005, 4:361-368.
• [33]Bauerschmidt C, Arrichiello C, Burdak-Rothkamm S, Woodcock M, Hill MA, Stevens DL, Rothkamm K: Cohesin promotes the repair of ionizing radiation-induced DNA double-strand breaks in replicated chromatin. Nucleic Acids Res 2010, 38:477-487.
• [34]Potts PR, Porteus MH, Yu H: Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. EMBO J 2006, 25:3377-3388.
• [35]Unal E, Arbel-Eden A, Sattler U, Shroff R, Lichten M, Haber JE, Koshland D: DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain. Mol Cell 2004, 16:991-1002.
• [36]Covo S, Westmoreland JW, Gordenin DA, Resnick MA: Cohesin Is limiting for the suppression of DNA damage-induced recombination between homologous chromosomes. PLoS Genet 2010, 6:e1001006.
• [37]Kim JS, Krasieva TB, LaMorte V, Taylor AM, Yokomori K: Specific recruitment of human cohesin to laser-induced DNA damage. J Biol Chem 2002, 277:45149-45153.
• [38]Strom L, Lindroos HB, Shirahige K, Sjogren C: Postreplicative recruitment of cohesin to double-strand breaks is required for DNA repair. Mol Cell 2004, 16:1003-1015.
• [39]Strom L, Karlsson C, Lindroos HB, Wedahl S, Katou Y, Shirahige K, Sjogren C: Postreplicative formation of cohesion is required for repair and induced by a single DNA break. Science 2007, 317:242-245.
• [40]Unal E, Heidinger-Pauli JM, Koshland D: DNA double-strand breaks trigger genome-wide sister-chromatid cohesion through Eco1 (Ctf7). Science 2007, 317:245-248.
• [41]Heidinger-Pauli JM, Unal E, Koshland D: Distinct targets of the Eco1 acetyltransferase modulate cohesion in S phase and in response to DNA damage. Mol Cell 2009, 34:311-321.
• [42]Heidinger-Pauli JM, Unal E, Guacci V, Koshland D: The kleisin subunit of cohesin dictates damage-induced cohesion. Mol Cell 2008, 31:47-56.
• [43]Dodson H, Morrison CG: Increased sister chromatid cohesion and DNA damage response factor localization at an enzyme-induced DNA double-strand break in vertebrate cells. Nucleic Acids Res 2009, 37:6054-6063.
• [44]Watanabe K, Pacher M, Dukowic S, Schubert V, Puchta H, Schubert I: The STRUCTURAL MAINTENANCE OF CHROMOSOMES 5/6 complex promotes sister chromatid alignment and homologous recombination after DNA damage in Arabidopsis thaliana. Plant Cell 2009, 21:2688-2699.
• [45]Kim BJ, Li Y, Zhang J, Xi Y, Yang T, Jung SY, Pan X, Chen R, Li W, Wang Y, et al.: Genome-wide reinforcement of cohesin binding at pre-existing cohesin sites in response to ionizing radiation in human cells. J Biol Chem 2010, 285:22784-22792.
• [46]Yazdi PT, Wang Y, Zhao S, Patel N, Lee EY, Qin J: SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Genes Dev 2002, 16:571-582.
• [47]Kim ST, Xu B, Kastan MB: Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage. Genes Dev 2002, 16:560-570.
• [48]Garg R, Callens S, Lim DS, Canman CE, Kastan MB, Xu B: Chromatin association of rad17 is required for an ataxia telangiectasia and rad-related kinase-mediated S-phase checkpoint in response to low-dose ultraviolet radiation. Mol Cancer Res 2004, 2:362-369.
• [49]Kitagawa R, Bakkenist CJ, McKinnon PJ, Kastan MB: Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev 2004, 18:1423-1438.
• [50]Luo H, Li Y, Mu JJ, Zhang J, Tonaka T, Hamamori Y, Jung SY, Wang Y, Qin J: Regulation of intra-S phase checkpoint by ionizing radiation (IR)-dependent and IR-independent phosphorylation of SMC3. J Biol Chem 2008, 283:19176-19183.
• [51]Watrin E, Peters JM: The cohesin complex is required for the DNA damage-induced G2/M checkpoint in mammalian cells. EMBO J 2009, 28:2625-2635.
• [52]Nagao K, Adachi Y, Yanagida M: Separase-mediated cleavage of cohesin at interphase is required for DNA repair. Nature 2004, 430:1044-1048.
• [53]Ono T, Losada A, Hirano M, Myers MP, Neuwald AF, Hirano T: Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells. Cell 2003, 115:109-121.
• [54]Hirano T: Chromosome shaping by two condensins. Cell Cycle 2004, 3:26-28.
• [55]Csankovszki G, Collette K, Spahl K, Carey J, Snyder M, Petty E, Patel U, Tabuchi T, Liu H, McLeod I, et al.: Three distinct condensin complexes control C. elegans chromosome dynamics. Curr Biol 2009, 19:9-19.
• [56]Aono N, Sutani T, Tomonaga T, Mochida S, Yanagida M: Cnd2 has dual roles in mitotic condensation and interphase. Nature 2002, 417:197-202.
• [57]Chen ES, Sutani T, Yanagida M: Cti1/C1D interacts with condensin SMC hinge and supports the DNA repair function of condensin. Proc Natl Acad Sci USA 2004, 101:8078-8083.
• [58]Heale JT, Ball AR Jr, Schmiesing JA, Kim JS, Kong X, Zhou S, Hudson DF, Earnshaw WC, Yokomori K: Condensin I interacts with the PARP-1-XRCC1 complex and functions in DNA single-strand break repair. Mol Cell 2006, 21:837-848.
• [59]Kong X, Stephens J, Ball AR Jr, Heale JT, Newkirk DA, Berns MW, Yokomori K: Condensin I recruitment to base damage-enriched DNA lesions is modulated by PARP1. PLoS One 2011, 6:e23548.
• [60]Wood JL, Liang Y, Li K, Chen J: Microcephalin/MCPH1 associates with the Condensin II complex to function in homologous recombination repair. J Biol Chem 2008, 283:29586-29592.
• [61]Tsang CK, Wei Y, Zheng XF: Compacting DNA during the interphase: condensin maintains rDNA integrity. Cell Cycle 2007, 6:2213-2218.
• [62]Tsang CK, Li H, Zheng XS: Nutrient starvation promotes condensin loading to maintain rDNA stability. EMBO J 2007, 26:448-458.
• [63]Tsang CK, Zheng XF: Opposing role of condensin and radiation-sensitive gene RAD52 in ribosomal DNA stability regulation. J Biol Chem 2009, 284:21908-21919.
• [64]Cabello OA, Eliseeva E, He WG, Youssoufian H, Plon SE, Brinkley BR, Belmont JW: Cell cycle-dependent expression and nucleolar localization of hCAP-H. Mol Biol Cell 2001, 12:3527-3537.
• [65]Uzbekov R, Timirbulatova E, Watrin E, Cubizolles F, Ogereau D, Gulak P, Legagneux V, Polyakov VJ, Le Guellec K, Kireev I: Nucleolar association of pEg7 and XCAP-E, two members of Xenopus laevis condensin complex in interphase cells. J Cell Sci 2003, 116:1667-1678.
• [66]Duan X, Yang Y, Chen YH, Arenz J, Rangi GK, Zhao X, Ye H: Architecture of the Smc5/6 Complex of Saccharomyces cerevisiae Reveals a Unique Interaction between the Nse5-6 Subcomplex and the Hinge Regions of Smc5 and Smc6. J Biol Chem 2009, 284:8507-8515.
• [67]Doyle JM, Gao J, Wang J, Yang M, Potts PR: MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases. Mol Cell 2010, 39:963-974.
• [68]Potts PR, Yu H: Human MMS21/NSE2 is a SUMO ligase required for DNA repair. Mol Cell Biol 2005, 25:7021-7032.
• [69]Andrews EA, Palecek J, Sergeant J, Taylor E, Lehmann AR, Watts FZ: Nse2, a component of the Smc5-6 complex, is a SUMO ligase required for the response to DNA damage. Mol Cell Biol 2005, 25:185-196.
• [70]Zhao X, Blobel G: A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc Natl Acad Sci USA 2005, 102:4777-4782.
• [71]Nasim A, Smith BP: Genetic control of radiation sensitivity in Schizosaccharomyces pombe. Genetics 1975, 79:573-582.
• [72]Lehmann AR, Walicka M, Griffiths DJ, Murray JM, Watts FZ, McCready S, Carr AM: The rad18 gene of Schizosaccharomyces pombe defines a new subgroup of the SMC superfamily involved in DNA repair. Mol Cell Biol 1995, 15:7067-7080.
• [73]Taylor EM, Copsey AC, Hudson JJ, Vidot S, Lehmann AR: Identification of the proteins, including MAGEG1, that make up the human SMC5-6 protein complex. Mol Cell Biol 2008, 28:1197-1206.
• [74]Santa Maria SR, Gangavarapu V, Johnson RE, Prakash L, Prakash S: Requirement of Nse1, a subunit of the Smc5-Smc6 complex, for Rad52-dependent postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Mol Cell Biol 2007, 27:8409-8418.
• [75]Pebernard S, Perry JJ, Tainer JA, Boddy MN: Nse1 RING-like domain supports functions of the Smc5-Smc6 holocomplex in genome stability. Mol Biol Cell 2008, 19:4099-4109.
• [76]Pebernard S, Wohlschlegel J, McDonald WH, Yates JR, Boddy MN: The Nse5-Nse6 dimer mediates DNA repair roles of the Smc5-Smc6 complex. Mol Cell Biol 2006, 26:1617-1630.
• [77]Verkade HM, Bugg SJ, Lindsay HD, Carr AM, O'Connell MJ: Rad18 is required for DNA repair and checkpoint responses in fission yeast. Mol Biol Cell 1999, 10:2905-2918.
• [78]McDonald WH, Pavlova Y, Yates JR, Boddy MN: Novel essential DNA repair proteins Nse1 and Nse2 are subunits of the fission yeast Smc5-Smc6 complex. J Biol Chem 2003, 278:45460-45467.
• [79]Stephan AK, Kliszczak M, Dodson H, Cooley C, Morrison CG: Roles of vertebrate Smc5 in sister chromatid cohesion and homologous recombinational repair. Mol Cell Biol 2011, 31:1369-1381.
• [80]De Piccoli G, Cortes-Ledesma F, Ira G, Torres-Rosell J, Uhle S, Farmer S, Hwang JY, Machin F, Ceschia A, McAleenan A, et al.: Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination. Nat Cell Biol 2006, 8:1032-1034.
• [81]Mengiste T, Revenkova E, Bechtold N, Paszkowski J: An SMC-like protein is required for efficient homologous recombination in Arabidopsis. EMBO J 1999, 18:4505-4512.
• [82]Lindroos HB, Strom L, Itoh T, Katou Y, Shirahige K, Sjogren C: Chromosomal association of the Smc5/6 complex reveals that it functions in differently regulated pathways. Mol Cell 2006, 22:755-767.
• [83]Ampatzidou E, Irmisch A, O'Connell MJ, Murray JM: Smc5/6 is required for repair at collapsed replication forks. Mol Cell Biol 2006, 26:9387-9401.
• [84]Branzei D, Sollier J, Liberi G, Zhao X, Maeda D, Seki M, Enomoto T, Ohta K, Foiani M: Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks. Cell 2006, 127:509-522.
• [85]Sheedy DM, Dimitrova D, Rankin JK, Bass KL, Lee KM, Tapia-Alveal C, Harvey SH, Murray JM, O'Connell MJ: Brc1-mediated DNA repair and damage tolerance. Genetics 2005, 171:457-468.
• [86]Lee KM, Nizza S, Hayes T, Bass KL, Irmisch A, Murray JM, O'Connell MJ: Brc1-mediated rescue of Smc5/6 deficiency: requirement for multiple nucleases and a novel Rad18 function. Genetics 2007, 175:1585-1595.
• [87]Chen YH, Choi K, Szakal B, Arenz J, Duan X, Ye H, Branzei D, Zhao X: Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. Proc Natl Acad Sci USA 2009, 106:21252-21257.
• [88]Bermudez-Lopez M, Ceschia A, de Piccoli G, Colomina N, Pasero P, Aragon L, Torres-Rosell J: The Smc5/6 complex is required for dissolution of DNA-mediated sister chromatid linkages. Nucleic Acids Res 2010, 38:6502-6512.
• [89]Chavez A, George V, Agrawal V, Johnson FB: Sumoylation and the structural maintenance of chromosomes (Smc) 5/6 complex slow senescence through recombination intermediate resolution. J Biol Chem 2010, 285:11922-11930.
• [90]Irmisch A, Ampatzidou E, Mizuno K, O'Connell MJ, Murray JM: Smc5/6 maintains stalled replication forks in a recombination-competent conformation. EMBO J 2009, 28:144-155.
• [91]Torres-Rosell J, Machin F, Farmer S, Jarmuz A, Eydmann T, Dalgaard JZ, Aragon L: SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions. Nat Cell Biol 2005, 7:412-419.
• [92]Torres-Rosell J, Machin F, Aragon L: Smc5-Smc6 complex preserves nucleolar integrity in S. cerevisiae. Cell Cycle 2005, 4:868-872.
• [93]Torres-Rosell J, Sunjevaric I, De Piccoli G, Sacher M, Eckert-Boulet N, Reid R, Jentsch S, Rothstein R, Aragon L, Lisby M: The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nat Cell Biol 2007, 9:923-931.