The checkpoint protein Zw10 connects CAL1-dependent CENP-A centromeric loading and mitosis duration in Drosophila cells


Autoři: Anne-Laure Pauleau aff001;  Andrea Bergner aff001;  Janko Kajtez aff001;  Sylvia Erhardt aff001
Působiště autorů: Center for Molecular Biology of Heidelberg University (ZMBH), Heidelberg, Germany aff001;  DKFZ-ZMBH-Alliance, Heidelberg, Germany aff002;  CellNetworks Excellence Cluster, Heidelberg University, Heidelberg, Germany aff003
Vyšlo v časopise: The checkpoint protein Zw10 connects CAL1-dependent CENP-A centromeric loading and mitosis duration in Drosophila cells. PLoS Genet 15(9): e32767. doi:10.1371/journal.pgen.1008380
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008380

Souhrn

A defining feature of centromeres is the presence of the histone H3 variant CENP-A that replaces H3 in a subset of centromeric nucleosomes. In Drosophila cultured cells CENP-A deposition at centromeres takes place during the metaphase stage of the cell cycle and strictly depends on the presence of its specific chaperone CAL1. How CENP-A loading is restricted to mitosis is unknown. We found that overexpression of CAL1 is associated with increased CENP-A levels at centromeres and uncouples CENP-A loading from mitosis. Moreover, CENP-A levels inversely correlate with mitosis duration suggesting crosstalk of CENP-A loading with the regulatory machinery of mitosis. Mitosis length is influenced by the spindle assembly checkpoint (SAC), and we found that CAL1 interacts with the SAC protein and RZZ complex component Zw10 and thus constitutes the anchor for the recruitment of RZZ. Therefore, CAL1 controls CENP-A incorporation at centromeres both quantitatively and temporally, connecting it to the SAC to ensure mitotic fidelity.

Klíčová slova:

Cell staining – DAPI staining – Drosophila melanogaster – Mitosis – Centromeres – Microtubules – Scanning electron microscopy – Immunofluorescence


Zdroje

1. Joglekar AP, Kukreja AA. How Kinetochore Architecture Shapes the Mechanisms of Its Function. Curr Biol. 2017;27(16):R816–R24. Epub 2017/08/23. doi: 10.1016/j.cub.2017.06.012 28829971.

2. Musacchio A, Desai A. A Molecular View of Kinetochore Assembly and Function. Biology (Basel). 2017;6(1). Epub 2017/01/27. doi: 10.3390/biology6010005 28125021.

3. Kapanidou M, Curtis NL, Bolanos-Garcia VM. Cdc20: At the Crossroads between Chromosome Segregation and Mitotic Exit. Trends Biochem Sci. 2017;42(3):193–205. Epub 2017/02/17. doi: 10.1016/j.tibs.2016.12.001 28202332.

4. Musacchio A. The Molecular Biology of Spindle Assembly Checkpoint Signaling Dynamics. Curr Biol. 2015;25(20):R1002–18. Epub 2015/10/21. doi: 10.1016/j.cub.2015.08.051 26485365.

5. Jansen LE, Black BE, Foltz DR, Cleveland DW. Propagation of centromeric chromatin requires exit from mitosis. J Cell Biol. 2007;176(6):795–805. Epub 2007/03/07. doi: 10.1083/jcb.200701066 17339380.

6. Takayama Y, Sato H, Saitoh S, Ogiyama Y, Masuda F, Takahashi K. Biphasic incorporation of centromeric histone CENP-A in fission yeast. Mol Biol Cell. 2008;19(2):682–90. Epub 2007/12/14. doi: 10.1091/mbc.E07-05-0504 18077559.

7. Shukla M, Tong P, White SA, Singh PP, Reid AM, Catania S, et al. Centromere DNA Destabilizes H3 Nucleosomes to Promote CENP-A Deposition during the Cell Cycle. Curr Biol. 2018;28(24):3924–36 e4. doi: 10.1016/j.cub.2018.10.049 30503616.

8. Lermontova I, Schubert V, Fuchs J, Klatte S, Macas J, Schubert I. Loading of Arabidopsis centromeric histone CENH3 occurs mainly during G2 and requires the presence of the histone fold domain. Plant Cell. 2006;18(10):2443–51. doi: 10.1105/tpc.106.043174 17028205.

9. Schuh M, Lehner CF, Heidmann S. Incorporation of Drosophila CID/CENP-A and CENP-C into centromeres during early embryonic anaphase. Curr Biol. 2007;17(3):237–43. Epub 2007/01/16. doi: 10.1016/j.cub.2006.11.051 17222555.

10. Mellone BG, Grive KJ, Shteyn V, Bowers SR, Oderberg I, Karpen GH. Assembly of Drosophila centromeric chromatin proteins during mitosis. PLoS Genet. 2011;7(5):e1002068. Epub 2011/05/19. doi: 10.1371/journal.pgen.1002068 21589899.

11. Dunleavy EM, Beier NL, Gorgescu W, Tang J, Costes SV, Karpen GH. The cell cycle timing of centromeric chromatin assembly in Drosophila meiosis is distinct from mitosis yet requires CAL1 and CENP-C. PLoS Biol. 2012;10(12):e1001460. doi: 10.1371/journal.pbio.1001460 23300382.

12. Lidsky PV, Sprenger F, Lehner CF. Distinct modes of centromere protein dynamics during cell cycle progression in Drosophila S2R+ cells. J Cell Sci. 2013;126(Pt 20):4782–93. Epub 2013/08/15. doi: 10.1242/jcs.134122 23943877.

13. Foltz DR, Jansen LE, Bailey AO, Yates JR 3rd, Bassett EA, Wood S, et al. Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP. Cell. 2009;137(3):472–84. Epub 2009/05/05. doi: 10.1016/j.cell.2009.02.039 19410544.

14. Camahort R, Li B, Florens L, Swanson SK, Washburn MP, Gerton JL. Scm3 is essential to recruit the histone h3 variant cse4 to centromeres and to maintain a functional kinetochore. Mol Cell. 2007;26(6):853–65. doi: 10.1016/j.molcel.2007.05.013 17569568.

15. Dunleavy EM, Roche D, Tagami H, Lacoste N, Ray-Gallet D, Nakamura Y, et al. HJURP is a cell-cycle-dependent maintenance and deposition factor of CENP-A at centromeres. Cell. 2009;137(3):485–97. Epub 2009/05/05. doi: 10.1016/j.cell.2009.02.040 19410545.

16. Mizuguchi G, Xiao H, Wisniewski J, Smith MM, Wu C. Nonhistone Scm3 and histones CenH3-H4 assemble the core of centromere-specific nucleosomes. Cell. 2007;129(6):1153–64. Epub 2007/06/19. doi: 10.1016/j.cell.2007.04.026 17574026.

17. Chen CC, Dechassa ML, Bettini E, Ledoux MB, Belisario C, Heun P, et al. CAL1 is the Drosophila CENP-A assembly factor. J Cell Biol. 2014;204(3):313–29. Epub 2014/01/29. doi: 10.1083/jcb.201305036 24469636.

18. Stoler S, Rogers K, Weitze S, Morey L, Fitzgerald-Hayes M, Baker RE. Scm3, an essential Saccharomyces cerevisiae centromere protein required for G2/M progression and Cse4 localization. Proc Natl Acad Sci U S A. 2007;104(25):10571–6. doi: 10.1073/pnas.0703178104 17548816.

19. Erhardt S, Mellone BG, Betts CM, Zhang W, Karpen GH, Straight AF. Genome-wide analysis reveals a cell cycle-dependent mechanism controlling centromere propagation. J Cell Biol. 2008;183(5):805–18. Epub 2008/12/03. doi: 10.1083/jcb.200806038 19047461.

20. Collins KA, Furuyama S, Biggins S. Proteolysis contributes to the exclusive centromere localization of the yeast Cse4/CENP-A histone H3 variant. Curr Biol. 2004;14(21):1968–72. Epub 2004/11/09. doi: 10.1016/j.cub.2004.10.024 15530401.

21. Hewawasam G, Shivaraju M, Mattingly M, Venkatesh S, Martin-Brown S, Florens L, et al. Psh1 is an E3 ubiquitin ligase that targets the centromeric histone variant Cse4. Mol Cell. 2010;40(3):444–54. Epub 2010/11/13. doi: 10.1016/j.molcel.2010.10.014 21070970.

22. Moreno-Moreno O, Torras-Llort M, Azorin F. Proteolysis restricts localization of CID, the centromere-specific histone H3 variant of Drosophila, to centromeres. Nucleic Acids Res. 2006;34(21):6247–55. Epub 2006/11/09. doi: 10.1093/nar/gkl902 17090596.

23. Heun P, Erhardt S, Blower MD, Weiss S, Skora AD, Karpen GH. Mislocalization of the Drosophila centromere-specific histone CID promotes formation of functional ectopic kinetochores. Dev Cell. 2006;10(3):303–15. Epub 2006/03/07. doi: 10.1016/j.devcel.2006.01.014 16516834.

24. Olszak AM, van Essen D, Pereira AJ, Diehl S, Manke T, Maiato H, et al. Heterochromatin boundaries are hotspots for de novo kinetochore formation. Nat Cell Biol. 2011;13(7):799–808. doi: 10.1038/ncb2272 21685892.

25. Muller S, Almouzni G. Chromatin dynamics during the cell cycle at centromeres. Nat Rev Genet. 2017;18(3):192–208. doi: 10.1038/nrg.2016.157 28138144.

26. Westermann S, Schleiffer A. Family matters: structural and functional conservation of centromere-associated proteins from yeast to humans. Trends Cell Biol. 2013;23(6):260–9. Epub 2013/03/14. doi: 10.1016/j.tcb.2013.01.010 23481674.

27. Heeger S, Leismann O, Schittenhelm R, Schraidt O, Heidmann S, Lehner CF. Genetic interactions of separase regulatory subunits reveal the diverged Drosophila Cenp-C homolog. Genes Dev. 2005;19(17):2041–53. doi: 10.1101/gad.347805 16140985.

28. Przewloka MR, Venkei Z, Bolanos-Garcia VM, Debski J, Dadlez M, Glover DM. CENP-C Is a Structural Platform for Kinetochore Assembly. Curr Biol. 2011;21(5):399–405. Epub 2011/03/01. doi: 10.1016/j.cub.2011.02.005 21353555.

29. Bade D, Pauleau AL, Wendler A, Erhardt S. The E3 ligase CUL3/RDX controls centromere maintenance by ubiquitylating and stabilizing CENP-A in a CAL1-dependent manner. Dev Cell. 2014;28(5):508–19. Epub 2014/03/19. doi: 10.1016/j.devcel.2014.01.031 24636256.

30. Schittenhelm RB, Althoff F, Heidmann S, Lehner CF. Detrimental incorporation of excess Cenp-A/Cid and Cenp-C into Drosophila centromeres is prevented by limiting amounts of the bridging factor Cal1. J Cell Sci. 2010;123(Pt 21):3768–79. Epub 2010/10/14. doi: 10.1242/jcs.067934 20940262.

31. Moreno-Moreno O, Medina-Giro S, Torras-Llort M, Azorin F. The F box protein partner of paired regulates stability of Drosophila centromeric histone H3, CenH3(CID). Curr Biol. 2011;21(17):1488–93. Epub 2011/08/30. doi: 10.1016/j.cub.2011.07.041 21871803.

32. Butkevich AN, Belov VN, Kolmakov K, Sokolov VV, Shojaei H, Sidenstein SC, et al. Hydroxylated Fluorescent Dyes for Live-Cell Labeling: Synthesis, Spectra and Super-Resolution STED. Chemistry. 2017;23(50):12114–9. Epub 2017/04/04. doi: 10.1002/chem.201701216 28370443.

33. Maia AF, Lopes CS, Sunkel CE. BubR1 and CENP-E have antagonistic effects upon the stability of microtubule-kinetochore attachments in Drosophila S2 cell mitosis. Cell Cycle. 2007;6(11):1367–78. doi: 10.4161/cc.6.11.4271 17525528.

34. Blower MD, Karpen GH. The role of Drosophila CID in kinetochore formation, cell-cycle progression and heterochromatin interactions. Nat Cell Biol. 2001;3(8):730–9. Epub 2001/08/03. doi: 10.1038/35087045 11483958.

35. Blower MD, Daigle T, Kaufman T, Karpen GH. Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components. PLoS Genet. 2006;2(7):e110. Epub 2006/07/15. doi: 10.1371/journal.pgen.0020110 16839185.

36. Orr B, Bousbaa H, Sunkel CE. Mad2-independent spindle assembly checkpoint activation and controlled metaphase-anaphase transition in Drosophila S2 cells. Mol Biol Cell. 2007;18(3):850–63. Epub 2006/12/22. doi: 10.1091/mbc.E06-07-0587 17182852.

37. Rahmani Z, Gagou ME, Lefebvre C, Emre D, Karess RE. Separating the spindle, checkpoint, and timer functions of BubR1. J Cell Biol. 2009;187(5):597–605. Epub 2009/12/03. doi: 10.1083/jcb.200905026 19951912.

38. Lince-Faria M, Maffini S, Orr B, Ding Y, Claudia F, Sunkel CE, et al. Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator. J Cell Biol. 2009;184(5):647–57. Epub 2009/03/11. doi: 10.1083/jcb.200811012 19273613.

39. Feijao T, Afonso O, Maia AF, Sunkel CE. Stability of kinetochore-microtubule attachment and the role of different KMN network components in Drosophila. Cytoskeleton (Hoboken). 2013;70(10):661–75. Epub 2013/08/21. doi: 10.1002/cm.21131 23959943.

40. Griffis ER, Stuurman N, Vale RD. Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore. J Cell Biol. 2007;177(6):1005–15. Epub 2007/06/20. doi: 10.1083/jcb.200702062 17576797.

41. Huang JY, Raff JW. The dynamic localisation of the Drosophila APC/C: evidence for the existence of multiple complexes that perform distinct functions and are differentially localised. J Cell Sci. 2002;115(Pt 14):2847–56. Epub 2002/06/26. 12082146.

42. Scaerou F, Starr DA, Piano F, Papoulas O, Karess RE, Goldberg ML. The ZW10 and Rough Deal checkpoint proteins function together in a large, evolutionarily conserved complex targeted to the kinetochore. J Cell Sci. 2001;114(Pt 17):3103–14. Epub 2001/10/09. 11590237.

43. Williams BC, Karr TL, Montgomery JM, Goldberg ML. The Drosophila l(1)zw10 gene product, required for accurate mitotic chromosome segregation, is redistributed at anaphase onset. J Cell Biol. 1992;118(4):759–73. Epub 1992/08/01. doi: 10.1083/jcb.118.4.759 1339459.

44. Williams BC, Goldberg ML. Determinants of Drosophila zw10 protein localization and function. J Cell Sci. 1994;107 (Pt 4):785–98. Epub 1994/04/01. 7914521.

45. Williams BC, Gatti M, Goldberg ML. Bipolar spindle attachments affect redistributions of ZW10, a Drosophila centromere/kinetochore component required for accurate chromosome segregation. J Cell Biol. 1996;134(5):1127–40. doi: 10.1083/jcb.134.5.1127 8794856.

46. Defachelles L, Raich N, Terracol R, Baudin X, Williams B, Goldberg M, et al. RZZ and Mad1 dynamics in Drosophila mitosis. Chromosome Res. 2015;23(2):333–42. Epub 2015/03/17. doi: 10.1007/s10577-015-9472-x 25772408.

47. Starr DA, Williams BC, Hays TS, Goldberg ML. ZW10 helps recruit dynactin and dynein to the kinetochore. J Cell Biol. 1998;142(3):763–74. Epub 1998/08/12. doi: 10.1083/jcb.142.3.763 9700164.

48. Wojcik E, Basto R, Serr M, Scaerou F, Karess R, Hays T. Kinetochore dynein: its dynamics and role in the transport of the Rough deal checkpoint protein. Nat Cell Biol. 2001;3(11):1001–7. Epub 2001/11/21. doi: 10.1038/ncb1101-1001 11715021.

49. Gassmann R, Essex A, Hu JS, Maddox PS, Motegi F, Sugimoto A, et al. A new mechanism controlling kinetochore-microtubule interactions revealed by comparison of two dynein-targeting components: SPDL-1 and the Rod/Zwilch/Zw10 complex. Genes Dev. 2008;22(17):2385–99. Epub 2008/09/04. doi: 10.1101/gad.1687508 18765790.

50. Buffin E, Lefebvre C, Huang J, Gagou ME, Karess RE. Recruitment of Mad2 to the kinetochore requires the Rod/Zw10 complex. Curr Biol. 2005;15(9):856–61. Epub 2005/05/12. doi: 10.1016/j.cub.2005.03.052 15886105.

51. Scaerou F, Aguilera I, Saunders R, Kane N, Blottiere L, Karess R. The rough deal protein is a new kinetochore component required for accurate chromosome segregation in Drosophila. J Cell Sci. 1999;112 (Pt 21):3757–68. Epub 1999/10/19. 10523511.

52. Basto R, Gomes R, Karess RE. Rough deal and Zw10 are required for the metaphase checkpoint in Drosophila. Nat Cell Biol. 2000;2(12):939–43. Epub 2001/01/09. doi: 10.1038/35046592 11146659.

53. Basto R, Scaerou F, Mische S, Wojcik E, Lefebvre C, Gomes R, et al. In vivo dynamics of the rough deal checkpoint protein during Drosophila mitosis. Curr Biol. 2004;14(1):56–61. Epub 2004/01/09. doi: 10.1016/j.cub.2003.12.025 14711415.

54. Williams BC, Li Z, Liu S, Williams EV, Leung G, Yen TJ, et al. Zwilch, a new component of the ZW10/ROD complex required for kinetochore functions. Mol Biol Cell. 2003;14(4):1379–91. Epub 2003/04/11. doi: 10.1091/mbc.E02-09-0624 12686595.

55. Karess RE, Glover DM. rough deal: a gene required for proper mitotic segregation in Drosophila. J Cell Biol. 1989;109(6 Pt 1):2951–61. Epub 1989/12/01. doi: 10.1083/jcb.109.6.2951 2512302.

56. Defachelles L, Hainline SG, Menant A, Lee LA, Karess RE. A maternal effect rough deal mutation suggests that multiple pathways regulate Drosophila RZZ kinetochore recruitment. J Cell Sci. 2015;128(15):2952. Epub 2015/08/05. doi: 10.1242/jcs.176826 26240166.

57. Wainman A, Giansanti MG, Goldberg ML, Gatti M. The Drosophila RZZ complex—roles in membrane trafficking and cytokinesis. J Cell Sci. 2012;125(Pt 17):4014–25. Epub 2012/06/12. doi: 10.1242/jcs.099820 22685323.

58. Przewloka MR, Zhang W, Costa P, Archambault V, D’Avino PP, Lilley KS, et al. Molecular analysis of core kinetochore composition and assembly in Drosophila melanogaster. PLoS One. 2007;2(5):e478. Epub 2007/05/31. doi: 10.1371/journal.pone.0000478 17534428.

59. Starr DA, Saffery R, Li Z, Simpson AE, Choo KH, Yen TJ, et al. HZwint-1, a novel human kinetochore component that interacts with HZW10. J Cell Sci. 2000;113 (Pt 11):1939–50. Epub 2000/05/12. 10806105.

60. Kops GJ, Kim Y, Weaver BA, Mao Y, McLeod I, Yates JR 3rd, et al. ZW10 links mitotic checkpoint signaling to the structural kinetochore. J Cell Biol. 2005;169(1):49–60. Epub 2005/04/13. doi: 10.1083/jcb.200411118 15824131.

61. Caldas GV, Lynch TR, Anderson R, Afreen S, Varma D, DeLuca JG. The RZZ complex requires the N-terminus of KNL1 to mediate optimal Mad1 kinetochore localization in human cells. Open Biol. 2015;5(11). Epub 2015/11/20. doi: 10.1098/rsob.150160 26581576.

62. Kasuboski JM, Bader JR, Vaughan PS, Tauhata SB, Winding M, Morrissey MA, et al. Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores. Mol Biol Cell. 2011;22(18):3318–30. Epub 2011/07/22. doi: 10.1091/mbc.E11-03-0213 21775627.

63. Zhang G, Lischetti T, Hayward DG, Nilsson J. Distinct domains in Bub1 localize RZZ and BubR1 to kinetochores to regulate the checkpoint. Nat Commun. 2015;6:7162. Epub 2015/06/03. doi: 10.1038/ncomms8162 26031201.

64. Schittenhelm RB, Chaleckis R, Lehner CF. Intrakinetochore localization and essential functional domains of Drosophila Spc105. EMBO J. 2009;28(16):2374–86. Epub 2009/07/11. doi: 10.1038/emboj.2009.188 19590494.

65. Orr B, Sunkel CE. Drosophila CENP-C is essential for centromere identity. Chromosoma. 2010;120(1):83–96. Epub 2010/09/24. doi: 10.1007/s00412-010-0293-6 20862486.

66. Basu J, Logarinho E, Herrmann S, Bousbaa H, Li Z, Chan GK, et al. Localization of the Drosophila checkpoint control protein Bub3 to the kinetochore requires Bub1 but not Zw10 or Rod. Chromosoma. 1998;107(6–7):376–85. Epub 1999/01/23. doi: 10.1007/s004120050321 9914369.

67. Lacoste N, Woolfe A, Tachiwana H, Garea AV, Barth T, Cantaloube S, et al. Mislocalization of the centromeric histone variant CenH3/CENP-A in human cells depends on the chaperone DAXX. Mol Cell. 2014;53(4):631–44. doi: 10.1016/j.molcel.2014.01.018 24530302.

68. Meraldi P, Draviam VM, Sorger PK. Timing and checkpoints in the regulation of mitotic progression. Dev Cell. 2004;7(1):45–60. Epub 2004/07/09. doi: 10.1016/j.devcel.2004.06.006 15239953.

69. Buffin E, Emre D, Karess RE. Flies without a spindle checkpoint. Nat Cell Biol. 2007;9(5):565–72. Epub 2007/04/10. doi: 10.1038/ncb1570 17417628.

70. Emre D, Terracol R, Poncet A, Rahmani Z, Karess RE. A mitotic role for Mad1 beyond the spindle checkpoint. J Cell Sci. 2011;124(Pt 10):1664–71. Epub 2011/04/23. doi: 10.1242/jcs.081216 21511728.

71. Li J, Dang N, Wood DJ, Huang JY. The kinetochore-dependent and -independent formation of the CDC20-MAD2 complex and its functions in HeLa cells. Sci Rep. 2017;7:41072. Epub 2017/01/24. doi: 10.1038/srep41072 28112196.

72. Sacristan C, Ahmad MUD, Keller J, Fermie J, Groenewold V, Tromer E, et al. Dynamic kinetochore size regulation promotes microtubule capture and chromosome biorientation in mitosis. Nat Cell Biol. 2018;20(7):800–10. Epub 2018/06/20. doi: 10.1038/s41556-018-0130-3 29915359.

73. Pereira C, Reis RM, Gama JB, Celestino R, Cheerambathur DK, Carvalho AX, et al. Self-Assembly of the RZZ Complex into Filaments Drives Kinetochore Expansion in the Absence of Microtubule Attachment. Curr Biol. 2018;28(21):3408–21 e8. doi: 10.1016/j.cub.2018.08.056 30415699.

74. Rodriguez-Rodriguez JA, Lewis C, McKinley KL, Sikirzhytski V, Corona J, Maciejowski J, et al. Distinct Roles of RZZ and Bub1-KNL1 in Mitotic Checkpoint Signaling and Kinetochore Expansion. Curr Biol. 2018;28(21):3422–9 e5. doi: 10.1016/j.cub.2018.10.006 30415700.

75. Schittenhelm RB, Heeger S, Althoff F, Walter A, Heidmann S, Mechtler K, et al. Spatial organization of a ubiquitous eukaryotic kinetochore protein network in Drosophila chromosomes. Chromosoma. 2007;116(4):385–402. Epub 2007/03/03. doi: 10.1007/s00412-007-0103-y 17333235.

76. Ahmad K, Henikoff S. Centromeres are specialized replication domains in heterochromatin. J Cell Biol. 2001;153(1):101–10. Epub 2001/04/04. doi: 10.1083/jcb.153.1.101 11285277.

77. Mathew V, Pauleau AL, Steffen N, Bergner A, Becker PB, Erhardt S. The histone-fold protein CHRAC14 influences chromatin composition in response to DNA damage. Cell Rep. 2014;7(2):321–30. Epub 2014/04/08. doi: 10.1016/j.celrep.2014.03.008 24703848.

78. Rothbauer U, Zolghadr K, Muyldermans S, Schepers A, Cardoso MC, Leonhardt H. A versatile nanotrap for biochemical and functional studies with fluorescent fusion proteins. Mol Cell Proteomics. 2008;7(2):282–9. Epub 2007/10/24. doi: 10.1074/mcp.M700342-MCP200 17951627.

79. Venkei Z, Przewloka MR, Glover DM. Drosophila Mis12 complex acts as a single functional unit essential for anaphase chromosome movement and a robust spindle assembly checkpoint. Genetics. 2011;187(1):131–40. doi: 10.1534/genetics.110.119628 20980244.

80. Schramm C, Elliott S, Shevchenko A, Schiebel E. The Bbp1p-Mps2p complex connects the SPB to the nuclear envelope and is essential for SPB duplication. EMBO J. 2000;19(3):421–33. Epub 2000/02/02. doi: 10.1093/emboj/19.3.421 10654940.

Štítky
Genetika Reprodukční medicína

Článek vyšel v časopise

PLOS Genetics


2019 Číslo 9

Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Hypertenze a hypercholesterolémie – synergický efekt léčby
nový kurz
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Úloha kombinovaných preparátů v léčbě arteriální hypertenze
Autoři: prof. MUDr. Martin Haluzík, DrSc.

Halitóza
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Terapie roztroušené sklerózy v kostce
Autoři: MUDr. Dominika Šťastná, Ph.D.

Všechny kurzy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se