NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase activity

EMBO Journal

Volumn 34, Issue 21, 2015, Pages 2604-2619

  Jacome, Ariana ^a   Gutierrez Martinez, Paula ^a   Schiavoni, Federica ^a   Tenaglia, Enrico ^a   Martine, Paula ^a   Rodríguez Acebes, Sara ^a   Lecona, Emilio ^a   Murga, Matilde ^a   Méndez, Juan ^a   Blasco, Maria A ^a   Fernandez Capetillo, Oscar ^a,b  

^a Structural Biology and Biocomputing Programme   (Spain)

^b KAROLINSKA INSTITUTE   (Sweden)

Author keywords

chromosome segregation; mouse models; NSMCE2; SMC5 6; SUMO

Indexed keywords

ADENOSINE TRIPHOSPHATASE; BLOOM SYNDROME HELICASE; BRCA1 PROTEIN; HISTONE H2A; MESYLIC ACID METHYL ESTER; NSMCE PROTEIN; SUMO LIGASE; UNCLASSIFIED DRUG; LIGASE; NSMCE2 PROTEIN, MOUSE; RECQ HELICASE; TUMOR SUPPRESSOR PROTEIN; UBIQUITIN PROTEIN LIGASE;

ADULT; AGING; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; B LYMPHOCYTE; CANCER INHIBITION; CHROMOSOME; CONTROLLED STUDY; DNA REPLICATION; DNA STRAND BREAKAGE; ENZYME ACTIVITY; HUMAN; IMMUNOFLUORESCENCE; MOUSE; NONHUMAN; PRIORITY JOURNAL; SUMOYLATION; WESTERN BLOTTING; 129 MOUSE; ANIMAL; C57BL MOUSE; CELL CULTURE; CHROMOSOME SEGREGATION; DNA MUTATIONAL ANALYSIS; DOUBLE STRANDED DNA BREAK; ENZYMOLOGY; FEMALE; HAPLOINSUFFICIENCY; KNOCKOUT MOUSE; METABOLISM; NEOPLASM; NUCLEOTIDE SEQUENCE; PHYSIOLOGY; PROTEIN TRANSPORT;

AGING; ANIMALS; B-LYMPHOCYTES; BASE SEQUENCE; CELLS, CULTURED; CHROMOSOME SEGREGATION; DNA BREAKS, DOUBLE-STRANDED; DNA MUTATIONAL ANALYSIS; DNA REPLICATION; FEMALE; HAPLOINSUFFICIENCY; HUMANS; LIGASES; MICE, 129 STRAIN; MICE, INBRED C57BL; MICE, KNOCKOUT; NEOPLASMS; PROTEIN TRANSPORT; RECQ HELICASES; SUMOYLATION; TUMOR SUPPRESSOR PROTEINS; UBIQUITIN-PROTEIN LIGASES;

EID: 84946099080     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.15252/embj.201591829     Document Type: Article

References (80)

1. Albuquerque CP, Wang G, Lee NS, Kolodner RD, Putnam CD, Zhou H, (2013) Distinct SUMO ligases cooperate with Esc2 and Slx5 to suppress duplication-mediated genome rearrangements. PLoS Genet 9: e1003670
2. Andrews EA, Palecek J, Sergeant J, Taylor E, Lehmann AR, Watts FZ, (2005) Nse2, a component of the Smc5-6 complex, is a SUMO ligase required for the response to DNA damage. Mol Cell Biol 25: 185-196
3. Barlow JH, Faryabi RB, Callen E, Wong N, Malhowski A, Chen HT, Gutierrez-Cruz G, Sun HW, McKinnon P, Wright G, Casellas R, Robbiani DF, Staudt L, Fernandez-Capetillo O, Nussenzweig A, (2013) Identification of early replicating fragile sites that contribute to genome instability. Cell 152: 620-632
4. Bermudez-Lopez M, Ceschia A, de Piccoli G, Colomina N, Pasero P, Aragon L, Torres-Rosell J, (2010) The Smc5/6 complex is required for dissolution of DNA-mediated sister chromatid linkages. Nucleic Acids Res 38: 6502-6512
5. Branzei D, Sollier J, Liberi G, Zhao X, Maeda D, Seki M, Enomoto T, Ohta K, Foiani M, (2006) Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks. Cell 127: 509-522
6. Bunting SF, Callen E, Wong N, Chen HT, Polato F, Gunn A, Bothmer A, Feldhahn N, Fernandez-Capetillo O, Cao L, Xu X, Deng CX, Finkel T, Nussenzweig M, Stark JM, Nussenzweig A, (2010) 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141: 243-254
7. Celeste A, Fernandez-Capetillo O, Kruhlak MJ, Pilch DR, Staudt DW, Lee A, Bonner RF, Bonner WM, Nussenzweig A, (2003) Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat Cell Biol 5: 675-679
8. Chan KL, North PS, Hickson ID, (2007) BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges. EMBO J 26: 3397-3409
9. Chan KL, Palmai-Pallag T, Ying S, Hickson ID, (2009) Replication stress induces sister-chromatid bridging at fragile site loci in mitosis. Nat Cell Biol 11: 753-760
10. Chavez A, George V, Agrawal V, Johnson FB, (2010) Sumoylation and the structural maintenance of chromosomes (Smc) 5/6 complex slow senescence through recombination intermediate resolution. J Biol Chem 285: 11922-11930
11. Chavez A, Agrawal V, Johnson FB, (2011) Homologous recombination-dependent rescue of deficiency in the structural maintenance of chromosomes (Smc) 5/6 complex. J Biol Chem 286: 5119-5125
12. Chen YH, Choi K, Szakal B, Arenz J, Duan X, Ye H, Branzei D, Zhao X, (2009) Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. Proc Natl Acad Sci USA 106: 21252-21257
13. Chester N, Babbe H, Pinkas J, Manning C, Leder P, (2006) Mutation of the murine Bloom's syndrome gene produces global genome destabilization. Mol Cell Biol 26: 6713-6726
14. Chinen Y, Sakamoto N, Nagoshi H, Taki T, Maegawa S, Tatekawa S, Tsukamoto T, Mizutani S, Shimura Y, Yamamoto-Sugitani M, Kobayashi T, Matsumoto Y, Horiike S, Kuroda J, Taniwaki M, (2014) 8q24 amplified segments involve novel fusion genes between NSMCE2 and long noncoding RNAs in acute myelogenous leukemia. J Hematol Oncol 7: 68
15. Chu WK, Hickson ID, (2009) RecQ helicases: multifunctional genome caretakers. Nat Rev Cancer 9: 644-654
16. Copsey A, Tang S, Jordan PW, Blitzblau HG, Newcombe S, Chan AC, Newnham L, Li Z, Gray S, Herbert AD, Arumugam P, Hochwagen A, Hunter N, Hoffmann E, (2013) Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions. PLoS Genet 9: e1004071
17. Cremona CA, Sarangi P, Yang Y, Hang LE, Rahman S, Zhao X, (2012) Extensive DNA damage-induced sumoylation contributes to replication and repair and acts in addition to the mec1 checkpoint. Mol Cell 45: 422-432
18. De Piccoli G, Cortes-Ledesma F, Ira G, Torres-Rosell J, Uhle S, Farmer S, Hwang JY, Machin F, Ceschia A, McAleenan A, Cordon-Preciado V, Clemente-Blanco A, Vilella-Mitjana F, Ullal P, Jarmuz A, Leitao B, Bressan D, Dotiwala F, Papusha A, Zhao X, et al, (2006) Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination. Nat Cell Biol 8: 1032-1034
19. De Piccoli G, Torres-Rosell J, Aragon L, (2009) The unnamed complex: what do we know about Smc5-Smc6? Chromosome Res 17: 251-263
20. Diderich K, Alanazi M, Hoeijmakers JH, (2011) Premature aging and cancer in nucleotide excision repair-disorders. DNA Repair 10: 772-780
21. Doyle JM, Gao J, Wang J, Yang M, Potts PR, (2010) MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases. Mol Cell 39: 963-974
22. Farmer S, San-Segundo PA, Aragon L, (2011) The Smc5-Smc6 complex is required to remove chromosome junctions in meiosis. PLoS ONE 6: e20948
23. Fernandez-Capetillo O, Mahadevaiah SK, Celeste A, Romanienko PJ, Camerini-Otero RD, Bonner WM, Manova K, Burgoyne P, Nussenzweig A, (2003) H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev Cell 4: 497-508
24. Fousteri MI, Lehmann AR, (2000) A novel SMC protein complex in Schizosaccharomyces pombe contains the Rad18 DNA repair protein. EMBO J 19: 1691-1702
25. Gallego-Paez LM, Tanaka H, Bando M, Takahashi M, Nozaki N, Nakato R, Shirahige K, Hirota T, (2014) Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells. Mol Biol Cell 25: 302-317
26. Gomez R, Jordan PW, Viera A, Alsheimer M, Fukuda T, Jessberger R, Llano E, Pendas AM, Handel MA, Suja JA, (2013) Dynamic localization of SMC5/6 complex proteins during mammalian meiosis and mitosis suggests functions in distinct chromosome processes. J Cell Sci 126: 4239-4252
27. Gonzalo S, Jaco I, Fraga MF, Chen T, Li E, Esteller M, Blasco MA, (2006) DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat Cell Biol 8: 416-424
28. Jackson DA, Pombo A, (1998) Replicon clusters are stable units of chromosome structure: evidence that nuclear organization contributes to the efficient activation and propagation of S phase in human cells. J Cell Biol 140: 1285-1295
29. Ju L, Wing J, Taylor E, Brandt R, Slijepcevic P, Horsch M, Rathkolb B, Racz I, Becker L, Hans W, Adler T, Beckers J, Rozman J, Klingenspor M, Wolf E, Zimmer A, Klopstock T, Busch DH, Gailus-Durner V, Fuchs H, et al, (2013) SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities. DNA Repair 12: 356-366
30. Kegel A, Betts-Lindroos H, Kanno T, Jeppsson K, Strom L, Katou Y, Itoh T, Shirahige K, Sjogren C, (2011) Chromosome length influences replication-induced topological stress. Nature 471: 392-396
31. Kliszczak M, Stephan AK, Flanagan AM, Morrison CG, (2012) SUMO ligase activity of vertebrate Mms21/Nse2 is required for efficient DNA repair but not for Smc5/6 complex stability. DNA Repair 11: 799-810
32. Lehmann AR, Walicka M, Griffiths DJ, Murray JM, Watts FZ, McCready S, Carr AM, (1995) The rad18 gene of Schizosaccharomyces pombe defines a new subgroup of the SMC superfamily involved in DNA repair. Mol Cell Biol 15: 7067-7080
33. Lilienthal I, Kanno T, Sjogren C, (2013) Inhibition of the Smc5/6 complex during meiosis perturbs joint molecule formation and resolution without significantly changing crossover or non-crossover levels. PLoS Genet 9: e1003898
34. Lindroos HB, Strom L, Itoh T, Katou Y, Shirahige K, Sjogren C, (2006) Chromosomal association of the Smc5/6 complex reveals that it functions in differently regulated pathways. Mol Cell 22: 755-767
35. Lopez-Contreras AJ, Fernandez-Capetillo O, (2010) The ATR barrier to replication-born DNA damage. DNA Repair 9: 1249-1255
36. Losada A, Hirano T, (2005) Dynamic molecular linkers of the genome: the first decade of SMC proteins. Genes Dev 19: 1269-1287
37. Mahadevaiah SK, Bourc'his D, de Rooij DG, Bestor TH, Turner JM, Burgoyne PS, (2008) Extensive meiotic asynapsis in mice antagonises meiotic silencing of unsynapsed chromatin and consequently disrupts meiotic sex chromosome inactivation. J Cell Biol 182: 263-276
38. Mankouri HW, Huttner D, Hickson ID, (2013) How unfinished business from S-phase affects mitosis and beyond. EMBO J 32: 2661-2671
39. McDonald WH, Pavlova Y, Yates JR III, Boddy MN, (2003) Novel essential DNA repair proteins Nse1 and Nse2 are subunits of the fission yeast Smc5-Smc6 complex. J Biol Chem 278: 45460-45467
40. McPherson JP, Lemmers B, Chahwan R, Pamidi A, Migon E, Matysiak-Zablocki E, Moynahan ME, Essers J, Hanada K, Poonepalli A, Sanchez-Sweatman O, Khokha R, Kanaar R, Jasin M, Hande MP, Hakem R, (2004) Involvement of mammalian Mus81 in genome integrity and tumor suppression. Science 304: 1822-1826
41. Morikawa H, Morishita T, Kawane S, Iwasaki H, Carr AM, Shinagawa H, (2004) Rad62 protein functionally and physically associates with the smc5/smc6 protein complex and is required for chromosome integrity and recombination repair in fission yeast. Mol Cell Biol 24: 9401-9413
42. Mouron S, Rodriguez-Acebes S, Martinez-Jimenez MI, Garcia-Gomez S, Chocron S, Blanco L, Mendez J, (2013) Repriming of DNA synthesis at stalled replication forks by human PrimPol. Nat Struct Mol Biol 20: 1383-1389
43. Murray JM, Carr AM, (2008) Smc5/6: a link between DNA repair and unidirectional replication? Nat Rev Mol Cell Biol 9: 177-182
44. Naim V, Rosselli F, (2009) The FANC pathway and BLM collaborate during mitosis to prevent micro-nucleation and chromosome abnormalities. Nat Cell Biol 11: 761-768
45. Nasim A, Smith BP, (1975) Genetic control of radiation sensitivity in Schizosaccharomyces pombe. Genetics 79: 573-582
46. Nasmyth K, Haering CH, (2005) The structure and function of SMC and kleisin complexes. Annu Rev Biochem 74: 595-648
47. Noel JF, Wellinger RJ, (2011) Abrupt telomere losses and reduced end-resection can explain accelerated senescence of Smc5/6 mutants lacking telomerase. DNA Repair 10: 271-282
48. Outwin EA, Irmisch A, Murray JM, O'Connell MJ, (2009) Smc5-Smc6-dependent removal of cohesin from mitotic chromosomes. Mol Cell Biol 29: 4363-4375
49. Palecek J, Vidot S, Feng M, Doherty AJ, Lehmann AR, (2006) The Smc5-Smc6 DNA repair complex. bridging of the Smc5-Smc6 heads by the KLEISIN, Nse4, and non-Kleisin subunits. J Biol Chem 281: 36952-36959
50. Payne F, Colnaghi R, Rocha N, Seth A, Harris J, Carpenter G, Bottomley WE, Wheeler E, Wong S, Saudek V, Savage D, O'Rahilly S, Carel JC, Barroso I, O'Driscoll M, Semple R, (2014) Hypomorphism in human NSMCE2 linked to primordial dwarfism and insulin resistance. J Clin Invest 124: 4028-4038
51. Pebernard S, McDonald WH, Pavlova Y, Yates JR III, Boddy MN, (2004) Nse1, Nse2, and a novel subunit of the Smc5-Smc6 complex, Nse3, play a crucial role in meiosis. Mol Biol Cell 15: 4866-4876
52. Pebernard S, Perry JJ, Tainer JA, Boddy MN, (2008a) Nse1 RING-like domain supports functions of the Smc5-Smc6 holocomplex in genome stability. Mol Biol Cell 19: 4099-4109
53. Pebernard S, Schaffer L, Campbell D, Head SR, Boddy MN, (2008b) Localization of Smc5/6 to centromeres and telomeres requires heterochromatin and SUMO, respectively. EMBO J 27: 3011-3023
54. Petermann E, Woodcock M, Helleday T, (2010) Chk1 promotes replication fork progression by controlling replication initiation. Proc Natl Acad Sci USA 107: 16090-16095
55. Potts PR, Yu H, (2005) Human MMS21/NSE2 is a SUMO ligase required for DNA repair. Mol Cell Biol 25: 7021-7032
56. Potts PR, Porteus MH, Yu H, (2006) Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. EMBO J 25: 3377-3388
57. Potts PR, Yu H, (2007) The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins. Nat Struct Mol Biol 14: 581-590
58. Prakash S, Prakash L, (1977) Increased spontaneous mitotic segregation in MMS-sensitive mutants of Saccharomyces cerevisiae. Genetics 87: 229-236
59. Rickert RC, Roes J, Rajewsky K, (1997) B lymphocyte-specific, Cre-mediated mutagenesis in mice. Nucleic Acids Res 25: 1317-1318
60. Rodriguez CI, Buchholz F, Galloway J, Sequerra R, Kasper J, Ayala R, Stewart AF, Dymecki SM, (2000) High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat Genet 25: 139-140
61. Rogakou EP, Boon C, Redon C, Bonner WM, (1999) Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 146: 905-916
62. Ruzankina Y, Pinzon-Guzman C, Asare A, Ong T, Pontano L, Cotsarelis G, Zediak VP, Velez M, Bhandoola A, Brown EJ, (2007) Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss. Cell Stem Cell 1: 113-126
63. Samper E, Goytisolo FA, Slijepcevic P, van Buul PP, Blasco MA, (2000) Mammalian Ku86 protein prevents telomeric fusions independently of the length of TTAGGG repeats and the G-strand overhang. EMBO Rep 1: 244-252
64. Scully R, Chen J, Ochs RL, Keegan K, Hoekstra M, Feunteun J, Livingston DM, (1997a) Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage. Cell 90: 425-435
65. Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM, (1997b) Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 88: 265-275
66. Sergeant J, Taylor E, Palecek J, Fousteri M, Andrews EA, Sweeney S, Shinagawa H, Watts FZ, Lehmann AR, (2005) Composition and architecture of the Schizosaccharomyces pombe Rad18 (Smc5-6) complex. Mol Cell Biol 25: 172-184
67. Stephan AK, Kliszczak M, Dodson H, Cooley C, Morrison CG, (2011a) Roles of vertebrate Smc5 in sister chromatid cohesion and homologous recombinational repair. Mol Cell Biol 31: 1369-1381
68. Stephan AK, Kliszczak M, Morrison CG, (2011b) The Nse2/Mms21 SUMO ligase of the Smc5/6 complex in the maintenance of genome stability. FEBS Lett 585: 2907-2913
69. 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
70. Tashiro S, Walter J, Shinohara A, Kamada N, Cremer T, (2000) Rad51 accumulation at sites of DNA damage and in postreplicative chromatin. J Cell Biol 150: 283-291
71. Taylor EM, Moghraby JS, Lees JH, Smit B, Moens PB, Lehmann AR, (2001) Characterization of a novel human SMC heterodimer homologous to the Schizosaccharomyces pombe Rad18/Spr18 complex. Mol Biol Cell 12: 1583-1594
72. Taylor EM, Copsey AC, Hudson JJ, Vidot S, Lehmann AR, (2008) Identification of the proteins, including MAGEG1, that make up the human SMC5-6 protein complex. Mol Cell Biol 28: 1197-1206
73. Torres-Rosell J, Machin F, Farmer S, Jarmuz A, Eydmann T, Dalgaard JZ, Aragon L, (2005) SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions. Nat Cell Biol 7: 412-419
74. Torres-Rosell J, De Piccoli G, Cordon-Preciado V, Farmer S, Jarmuz A, Machin F, Pasero P, Lisby M, Haber JE, Aragon L, (2007) Anaphase onset before complete DNA replication with intact checkpoint responses. Science 315: 1411-1415
75. Verkade HM, Bugg SJ, Lindsay HD, Carr AM, O'Connell MJ, (1999) Rad18 is required for DNA repair and checkpoint responses in fission yeast. Mol Biol Cell 10: 2905-2918
76. Verver DE, Langedijk NS, Jordan PW, Repping S, Hamer G, (2014) The SMC5/6 Complex is involved in crucial processes during human spermatogenesis. Biol Reprod 91: 22
77. Wechsler T, Newman S, West SC, (2011) Aberrant chromosome morphology in human cells defective for Holliday junction resolution. Nature 471: 642-646
78. Wu N, Kong X, Ji Z, Zeng W, Potts PR, Yokomori K, Yu H, (2012) Scc1 sumoylation by Mms21 promotes sister chromatid recombination through counteracting Wapl. Genes Dev 26: 1473-1485
79. Xaver M, Huang L, Chen D, Klein F, (2013) Smc5/6-mms21 prevents and eliminates inappropriate recombination intermediates in meiosis. PLoS Genet 9: e1004067
80. Zhao X, Blobel G, (2005) A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc Natl Acad Sci USA 102: 4777-4782