A Conserved Domain in the Scc3 Subunit of Cohesin Mediates the Interaction with Both Mcd1 and the Cohesin Loader Complex

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Cohesin is a four-subunit complex that tethers distinct regions of chromatin either intra- or inter-molecularly. Cohesin is essential for mediating proper chromosome structure and dynamics and to maintain genome stability. In humans, mutations in cohesin are associated with several developmental disorders and cancer. The function of the Scc3 subunit of cohesin is unclear. In this study we use a genetic approach to isolate mutations in SCC3 that abrogate cohesin function. We identified a mutant adjacent to an evolutionarily conserved domain of Scc3 termed the SCD. This mutant retained the ability to interact with the cohesin loader and the cohesin regulatory proteins Wpl1 and Pds5. However, it abrogated the interaction with the cohesin core trimer (Mcd1, Smc1, Smc3). This interaction was found to be critical for the initial association of cohesin with chromosomes and for its tethering activity. In-depth analyses of the SCD revealed a subset of mutants that retained their ability to interact with the cohesin trimer and had normal cohesion but were inviable and defective for condensation. These results reveal that the SCD region of Scc3 plays a role in chromosome condensation distinct from that in cohesion. Our results shed a new light on the mechanisms whereby cohesin helps maintains genome stability.

Vyšlo v časopise: A Conserved Domain in the Scc3 Subunit of Cohesin Mediates the Interaction with Both Mcd1 and the Cohesin Loader Complex. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005036
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005036

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Zdroje

1. Onn I, Heidinger-Pauli JM, Guacci V, Unal E, Koshland DE (2008) Sister chromatid cohesion: a simple concept with a complex reality. Annu Rev Cell Dev Biol 24: 105–129. doi: 10.1146/annurev.cellbio.24.110707.175350 18616427

2. Nasmyth K, Haering CH (2009) Cohesin: its roles and mechanisms. Annu Rev Genet 43: 525–558. doi: 10.1146/annurev-genet-102108-134233 19886810

3. Guacci V, Koshland D, Strunnikov A (1997) A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. cerevisiae. Cell 91: 47–57. 9335334

4. Losada A, Hirano M, Hirano T (1998) Identification of Xenopus SMC protein complexes required for sister chromatid cohesion. Genes Dev 12: 1986–1997. 9649503

5. Michaelis C, Ciosk R, Nasmyth K (1997) Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell 91: 35–45. 9335333

6. Sumara I, Vorlaufer E, Gieffers C, Peters BH, Peters JM (2000) Characterization of vertebrate cohesin complexes and their regulation in prophase. J Cell Biol 151: 749–762. 11076961

7. Tomonaga T, Nagao K, Kawasaki Y, Furuya K, Murakami A, et al. (2000) Characterization of fission yeast cohesin: essential anaphase proteolysis of Rad21 phosphorylated in the S phase. Genes Dev 14: 2757–2770. 11069892

8. Jessberger R (2002) The many functions of SMC proteins in chromosome dynamics. Nat Rev Mol Cell Biol 3: 767–778. 12360193

9. Donze D, Adams CR, Rine J, Kamakaka RT (1999) The boundaries of the silenced HMR domain in Saccharomyces cerevisiae. Genes Dev 13: 698–708. 10090726

10. Dorsett D (2007) Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromes. Chromosoma 116: 1–13. 16819604

11. Schaaf CA, Misulovin Z, Sahota G, Siddiqui AM, Schwartz YB, et al. (2009) Regulation of the Drosophila Enhancer of split and invected-engrailed gene complexes by sister chromatid cohesion proteins. PLoS One 4: e6202. doi: 10.1371/journal.pone.0006202 19587787

12. Strom L, Karlsson C, Lindroos HB, Wedahl S, Katou Y, et al. (2007) Postreplicative formation of cohesion is required for repair and induced by a single DNA break. Science 317: 242–245. 17626884

13. Unal E, Heidinger-Pauli JM, Koshland D (2007) DNA double-strand breaks trigger genome-wide sister-chromatid cohesion through Eco1 (Ctf7). Science 317: 245–248. 17626885

14. Liu J, Krantz ID (2008) Cohesin and human disease. Annu Rev Genomics Hum Genet 9: 303–320. doi: 10.1146/annurev.genom.9.081307.164211 18767966

15. Mannini L, Musio A (2011) The dark side of cohesin: the carcinogenic point of view. Mutat Res 728: 81–87. 22106471

16. McNairn AJ, Gerton JL (2008) Cohesinopathies: One ring, many obligations. Mutat Res 647: 103–111. doi: 10.1016/j.mrfmmm.2008.08.010 18786550

17. Toth A, Ciosk R, Uhlmann F, Galova M, Schleiffer A, et al. (1999) Yeast cohesin complex requires a conserved protein, Eco1p(Ctf7), to establish cohesion between sister chromatids during DNA replication. Genes Dev 13: 320–333. 9990856

18. Rollins RA, Morcillo P, Dorsett D (1999) Nipped-B, a Drosophila homologue of chromosomal adherins, participates in activation by remote enhancers in the cut and Ultrabithorax genes. Genetics 152: 577–593. 10353901

19. Losada A, Yokochi T, Kobayashi R, Hirano T (2000) Identification and characterization of SA/Scc3p subunits in the Xenopus and human cohesin complexes. J Cell Biol 150: 405–416. 10931856

20. Remeseiro S, Cuadrado A, Carretero M, Martinez P, Drosopoulos WC, et al. (2012) Cohesin-SA1 deficiency drives aneuploidy and tumourigenesis in mice due to impaired replication of telomeres. EMBO J 31: 2076–2089. doi: 10.1038/emboj.2012.11 22415365

21. Haering CH, Lowe J, Hochwagen A, Nasmyth K (2002) Molecular architecture of SMC proteins and the yeast cohesin complex. Mol Cell 9: 773–788. 11983169

22. Gandhi R, Gillespie PJ, Hirano T (2006) Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase. Curr Biol 16: 2406–2417. 17112726

23. Rowland BD, Roig MB, Nishino T, Kurze A, Uluocak P, et al. (2009) Building sister chromatid cohesion: smc3 acetylation counteracts an antiestablishment activity. Mol Cell 33: 763–774. doi: 10.1016/j.molcel.2009.02.028 19328069

24. Sutani T, Kawaguchi T, Kanno R, Itoh T, Shirahige K (2009) Budding yeast Wpl1(Rad61)-Pds5 complex counteracts sister chromatid cohesion-establishing reaction. Curr Biol 19: 492–497. doi: 10.1016/j.cub.2009.01.062 19268589

25. Ciosk R, Shirayama M, Shevchenko A, Tanaka T, Toth A, et al. (2000) Cohesin's binding to chromosomes depends on a separate complex consisting of Scc2 and Scc4 proteins. Mol Cell 5: 243–254. 10882066

26. Murayama Y, Uhlmann F (2014) Biochemical reconstitution of topological DNA binding by the cohesin ring. Nature 505: 367–371. doi: 10.1038/nature12867 24291789

27. Hartman T, Stead K, Koshland D, Guacci V (2000) Pds5p is an essential chromosomal protein required for both sister chromatid cohesion and condensation in Saccharomyces cerevisiae. J Cell Biol 151: 613–626. 11062262

28. Panizza S, Tanaka T, Hochwagen A, Eisenhaber F, Nasmyth K (2000) Pds5 cooperates with cohesin in maintaining sister chromatid cohesion. Curr Biol 10: 1557–1564. 11137006

29. Hunter S, Jones P, Mitchell A, Apweiler R, Attwood TK, et al. (2012) InterPro in 2011: new developments in the family and domain prediction database. Nucleic Acids Res 40: D306–312. doi: 10.1093/nar/gkr948 22096229

30. Zhang N, Jiang Y, Mao Q, Demeler B, Tao YJ, et al. (2013) Characterization of the interaction between the cohesin subunits Rad21 and SA1/2. PLoS One 8: e69458. doi: 10.1371/journal.pone.0069458 23874961

31. Bermudez VP, Farina A, Higashi TL, Du F, Tappin I, et al. (2012) In vitro loading of human cohesin on DNA by the human Scc2-Scc4 loader complex. Proc Natl Acad Sci U S A 109: 9366–9371. doi: 10.1073/pnas.1206840109 22628566

32. Rolef Ben-Shahar T, Heeger S, Lehane C, East P, Flynn H, et al. (2008) Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion. Science 321: 563–566. doi: 10.1126/science.1157774 18653893

33. Unal E, Heidinger-Pauli JM, Kim W, Guacci V, Onn I, et al. (2008) A molecular determinant for the establishment of sister chromatid cohesion. Science 321: 566–569. doi: 10.1126/science.1157880 18653894

34. Guacci V, Stricklin J, Bloom MS, Guo X, Bhatter M, et al. (2014) A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyl-transferase. Mol Biol Cell.

35. Guacci V, Koshland D (2012) Cohesin-independent segregation of sister chromatids in budding yeast. Mol Biol Cell 23: 729–739. doi: 10.1091/mbc.E11-08-0696 22190734

36. Milutinovich M, Unal E, Ward C, Skibbens RV, Koshland D (2007) A multi-step pathway for the establishment of sister chromatid cohesion. PLoS Genet 3: e12. 17238288

37. Eng T, Guacci V, Koshland D (2014) ROCC, a conserved region in cohesin's Mcd1 subunit, is essential for the proper regulation of the maintenance of cohesion and establishment of condensation. Mol Biol Cell 25: 2351–2364. doi: 10.1091/mbc.E14-04-0929 24966169

38. Nishimura K, Fukagawa T, Takisawa H, Kakimoto T, Kanemaki M (2009) An auxin-based degron system for the rapid depletion of proteins in nonplant cells. Nat Methods 6: 917–922. doi: 10.1038/nmeth.1401 19915560

39. Morawska M, Ulrich HD (2013) An expanded tool kit for the auxin-inducible degron system in budding yeast. Yeast 30: 341–351. doi: 10.1002/yea.2967 23836714

40. Roig MB, Lowe J, Chan KL, Beckouet F, Metson J, et al. (2014) Structure and function of cohesin's Scc3/SA regulatory subunit. FEBS Lett 588: 3692–3702. doi: 10.1016/j.febslet.2014.08.015 25171859

41. Lavoie BD, Hogan E, Koshland D (2002) In vivo dissection of the chromosome condensation machinery: reversibility of condensation distinguishes contributions of condensin and cohesin. J Cell Biol 156: 805–815. 11864994

42. Stephens AD, Haase J, Vicci L, Taylor RM 2nd, Bloom K (2011) Cohesin, condensin, and the intramolecular centromere loop together generate the mitotic chromatin spring. J Cell Biol 193: 1167–1180. doi: 10.1083/jcb.201103138 21708976

43. Hirano M, Hirano T (2006) Opening closed arms: long-distance activation of SMC ATPase by hinge-DNA interactions. Mol Cell 21: 175–186. 16427008

44. Moreno-Herrero F, de Jager M, Dekker NH, Kanaar R, Wyman C, et al. (2005) Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA. Nature 437: 440–443. 16163361

45. Heidinger-Pauli JM, Mert O, Davenport C, Guacci V, Koshland D (2010) Systematic reduction of cohesin differentially affects chromosome segregation, condensation, and DNA repair. Curr Biol 20: 957–963. doi: 10.1016/j.cub.2010.04.018 20451387

46. Canudas S, Smith S (2009) Differential regulation of telomere and centromere cohesion by the Scc3 homologues SA1 and SA2, respectively, in human cells. J Cell Biol 187: 165–173. doi: 10.1083/jcb.200903096 19822671

47. Guthrie C, Fink GRE (1991) Guide to Yeast Genetics and Molecular Biology: Academic Press, New York.

48. Heidinger-Pauli JM, Unal E, Guacci V, Koshland D (2008) The kleisin subunit of cohesin dictates damage-induced cohesion. Mol Cell 31: 47–56. doi: 10.1016/j.molcel.2008.06.005 18614046