Polo kinase recruitment via the constitutive centromere-associated network at the kinetochore elevates centromeric RNA

Autoři: Guðjón Ólafsson aff001;  Peter H. Thorpe aff001
Působiště autorů: School of Biological and Chemical Sciences, Queen Mary, University of London, London, United Kingdom aff001
Vyšlo v časopise: Polo kinase recruitment via the constitutive centromere-associated network at the kinetochore elevates centromeric RNA. PLoS Genet 16(8): e32767. doi:10.1371/journal.pgen.1008990
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008990


The kinetochore, a multi-protein complex assembled on centromeres, is essential to segregate chromosomes during cell division. Deficiencies in kinetochore function can lead to chromosomal instability and aneuploidy—a hallmark of cancer cells. Kinetochore function is controlled by recruitment of regulatory proteins, many of which have been documented, however their function often remains uncharacterized and many are yet to be identified. To identify candidates of kinetochore regulation we used a proteome-wide protein association strategy in budding yeast and detected many proteins that are involved in post-translational modifications such as kinases, phosphatases and histone modifiers. We focused on the Polo-like kinase, Cdc5, and interrogated which cellular components were sensitive to constitutive Cdc5 localization. The kinetochore is particularly sensitive to constitutive Cdc5 kinase activity. Targeting Cdc5 to different kinetochore subcomplexes produced diverse phenotypes, consistent with multiple distinct functions at the kinetochore. We show that targeting Cdc5 to the inner kinetochore, the constitutive centromere-associated network (CCAN), increases the levels of centromeric RNA via an SPT4 dependent mechanism.

Klíčová slova:

Centromeres – Metaphase – Phenotypes – Phosphorylation – Saccharomyces cerevisiae – Suppressor genes – Yeast – Anaphase


1. Biggins S. The composition, functions, and regulation of the budding yeast kinetochore. Genetics. 2013;194: 817–846. doi: 10.1534/genetics.112.145276 23908374

2. Yan K, Yang J, Zhang Z, McLaughlin SH, Chang L, Fasci D, et al. Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome. Nature. 2019;574: 278–282. doi: 10.1038/s41586-019-1609-1 31578520

3. Hinshaw SM, Harrison SC. The structure of the ctf19c/ccan from budding yeast. Elife. 2019;8: 1–21. doi: 10.7554/eLife.44239 30762520

4. Hamilton G, Dimitrova Y, Davis TN. Seeing is believing: our evolving view of kinetochore structure, composition, and assembly. Curr Opin Cell Biol. 2019;60: 44–52. doi: 10.1016/j.ceb.2019.03.016 31078123

5. Kitamura E, Tanaka K, Kitamura Y, Tanaka TU. Kinetochore-microtubule interaction during S phase in Saccharomyces cerevisiae. Genes Dev. 2007;21: 3319–3330. doi: 10.1101/gad.449407 18079178

6. Wisniewski J, Hajj B, Chen J, Mizuguchi G, Xiao H, Wei D, et al. Imaging the fate of histone Cse4 reveals de novo replacement in S phase and subsequent stable residence at centromeres. Elife. 2014;2014: e02203. doi: 10.7554/eLife.02203 24844245

7. Musacchio A. The Molecular Biology of Spindle Assembly Checkpoint Signaling Dynamics. Curr Biol. 2015;25: R1002–R1018. doi: 10.1016/j.cub.2015.08.051 26485365

8. Joglekar AP. A cell biological perspective on past, present and future investigations of the spindle assembly checkpoint. Biology (Basel). 2016;5: 44. doi: 10.3390/biology5040044 27869759

9. Corbett KD. Molecular Mechanisms of Spindle Assembly Checkpoint Activation and Silencing. Progress in molecular and subcellular biology. Springer, Cham; 2017. pp. 429–455. doi: 10.1007/978-3-319-58592-5_18 28840248

10. Saurin AT. Kinase and phosphatase cross-talk at the kinetochore. Front Cell Dev Biol. 2018;6: 62. doi: 10.3389/fcell.2018.00062 29971233

11. Pinsky BA, Nelson CR, Biggins S. Checkpoint in Budding Yeast. Curr Biol. 2010;19: 1182–1187. doi: 10.1016/j.cub.2009.06.043.Protein

12. Liu D, Vleugel M, Backer CB, Hori T, Fukagawa T, Cheeseman IM, et al. Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase. J Cell Biol. 2010;188: 809–820. doi: 10.1083/jcb.201001006 20231380

13. Rosenberg JS, Cross FR, Funabiki H. KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint. Curr Biol. 2011;21: 942–947. doi: 10.1016/j.cub.2011.04.011 21640906

14. London N, Ceto S, Ranish JA, Biggins S. Phosphoregulation of Spc105 by Mps1 and PP1 regulates Bub1 localization to kinetochores. Curr Biol. 2012;22: 900–906. doi: 10.1016/j.cub.2012.03.052 22521787

15. Funabiki H, Wynne DJ. Making an effective switch at the kinetochore by phosphorylation and dephosphorylation. Chromosoma. 2013;122: 135–158. doi: 10.1007/s00412-013-0401-5 23512483

16. Zhang J, Wan L, Dai X, Sun Y, Wei W. Functional characterization of Anaphase Promoting Complex/Cyclosome (APC/C) E3 ubiquitin ligases in tumorigenesis. Biochim Biophys Acta—Rev Cancer. 2014;1845: 277–293. doi: 10.1016/j.bbcan.2014.02.001 24569229

17. Espert A, Uluocak P, Bastos RN, Mangat D, Graab P, Gruneberg U. PP2A-B56 opposes Mps1 phosphorylation of Knl1 and thereby promotes spindle assembly checkpoint silencing. J Cell Biol. 2014;206: 833–842. doi: 10.1083/jcb.201406109 25246613

18. Ólafsson G, Thorpe PH. Synthetic physical interactions map kinetochore regulators and regions sensitive to constitutive Cdc14 localization. Proc Natl Acad Sci U S A. 2015;112: 10413–10418. doi: 10.1073/pnas.1506101112 26240346

19. Daigaku Y, Keszthelyi A, Miyabe I, Ptasin K, Naiman K, Carr AM. Genome Instability. In: Muzi-Falconi M, Brown GW, editors. Genome Instability: Methods and Protocols. Humana Press Inc; 2018. pp. 239–259. doi: 10.1007/978-1-4939-7306-4

20. Berry LK, Ólafsson G, Ledesma-Fernández E, Thorpe PH. Synthetic protein interactions reveal a functional map of the cell. Elife. 2016;5. doi: 10.7554/eLife.13053 27098839

21. Howell RSM, Csikász-Nagy A, Thorpe PH. Synthetic physical interactions with the yeast centrosome. G3 Genes, Genomes, Genet. 2019;9: 2183–2194. doi: 10.1534/g3.119.400117 31076383

22. Ólafsson G, Thorpe PH. Synthetic physical interactions map kinetochore-checkpoint activation regions. G3 Genes, Genomes, Genet. 2016;6: 2531–2542. doi: 10.1534/g3.116.031930 27280788

23. Archambault V, Glover DM. Polo-like kinases: Conservation and divergence in their functions and regulation. Nat Rev Mol Cell Biol. 2009;10: 265–275. doi: 10.1038/nrm2653 19305416

24. Park JE, Soung NK, Johmura Y, Kang YH, Liao C, Lee KH, et al. Polo-box domain: a versatile mediator of polo-like kinase function. Cell Mol Life Sci. 2010;67: 1957–1970. doi: 10.1007/s00018-010-0279-9 20148280

25. Snead JL, Sullivan M, Lowery DM, Cohen MS, Zhang C, Randle DH, et al. A Coupled Chemical-Genetic and Bioinformatic Approach to Polo-like Kinase Pathway Exploration. Chem Biol. 2007;14: 1261–1272. doi: 10.1016/j.chembiol.2007.09.011 18022565

26. Mishra PK, Ciftci-Yilmaz S, Reynolds D, Au WC, Boeckmann L, Dittman LE, et al. Polo kinase Cdc5 associates with centromeres to facilitate the removal of centromeric cohesin during mitosis. Mol Biol Cell. 2016;27: 2286–2300. doi: 10.1091/mbc.E16-01-0004 27226485

27. Mishra PK, Olafsson G, Boeckmann L, Westlake TJ, Jowhar ZM, Dittman LE, et al. Cell cycle-dependent association of polo kinase Cdc5 with CENP-A contributes to faithful chromosome segregation in budding yeast. Mol Biol Cell. 2019;30: 1020–1036. doi: 10.1091/mbc.E18-09-0584 30726152

28. Park J-E, Park CJ, Sakchaisri K, Karpova T, Asano S, McNally J, et al. Novel Functional Dissection of the Localization-Specific Roles of Budding Yeast Polo Kinase Cdc5p. Mol Cell Biol. 2004;24: 9873–9886. doi: 10.1128/MCB.24.22.9873-9886.2004 15509790

29. Park CJ, Song S, Giddings TH, Ro HS, Sakchaisri K, Park JE, et al. Requirement for Bbp1p in the Proper Mitotic Functions of Cdc5p in Saccharomyces cerevisiae. Mol Biol Cell. 2004;15: 1711–1723. doi: 10.1091/mbc.e03-07-0461 14767068

30. Lera RF, Potts GK, Suzuki A, Johnson JM, Salmon ED, Coon JJ, et al. Decoding Polo-like kinase 1 signaling along the kinetochore-centromere axis. Nat Chem Biol. 2016;12: 411–418. doi: 10.1038/nchembio.2060 27043190

31. Lera RF, Norman RX, Dumont M, Dennee A, Martin-Koob J, Fachinetti D, et al. Plk1 protects kinetochore–centromere architecture against microtubule pulling forces. EMBO Rep. 2019;20: 1–16. doi: 10.15252/embr.201948711 31468671

32. Rothbauer U, Zolghadr K, Tillib S, Nowak D, Schermelleh L, Gahl A, et al. Targeting and tracing antigens in live cells with fluorescent nanobodies. Nat Methods. 2006/10/25. 2006;3: 887–889. doi: 10.1038/nmeth953 17060912

33. Huh WK, Falvo J V., Gerke LC, Carroll AS, Howson RW, Weissman JS, et al. Global analysis of protein localization in budding yeast. Nature. 2003/10/17. 2003;425: 686–691. doi: 10.1038/nature02026 14562095

34. Aravamudhan P, Goldfarb AA, Joglekar AP. The kinetochore encodes a mechanical switch to disrupt spindle assembly checkpoint signalling. Nat Cell Biol. 2015;17: 868–879. doi: 10.1038/ncb3179 26053220

35. Ito D, Saito Y, Matsumoto T. Centromere-tethered Mps1 pombe homolog (Mph1) kinase is a sufficient marker for recruitment of the spindle checkpoint protein Bub1, but not Mad1. Proc Natl Acad Sci U S A. 2012;109: 209–214. doi: 10.1073/pnas.1114647109 22184248

36. Costanzo M, VanderSluis B, Koch EN, Baryshnikova A, Pons C, Tan G, et al. A global genetic interaction network maps a wiring diagram of cellular function. Science. 2016;353: aaf1420–aaf1420. doi: 10.1126/science.aaf1420 27708008

37. Usaj M, Tan Y, Wang W, VanderSluis B, Zou A, Myers CL, et al. TheCellMap.org: A web-accessible database for visualizing and mining the global yeast genetic interaction network. G3 Genes, Genomes, Genet. 2017;7: 1539–1549. doi: 10.1534/g3.117.040220 28325812

38. Baryshnikova A. Systematic Functional Annotation and Visualization of Biological Networks. Cell Syst. 2016;2: 412–421. doi: 10.1016/j.cels.2016.04.014 27237738

39. Wong J, Nakajima Y, Westermann S, Shang C, Kang JS, Goodner C, et al. A protein interaction map of the mitotic spindle. Mol Biol Cell. 2007;18: 3800–3809. doi: 10.1091/mbc.e07-06-0536 17634282

40. Park CJ, Park JE, Karpova TS, Soung NK, Yu LR, Song S, et al. Requirement for the budding yeast polo kinase Cdc5 in proper microtubule growth and dynamics. Eukaryot Cell. 2008;7: 444–453. doi: 10.1128/EC.00283-07 18178775

41. Rancati G, Crispo V, Lucchini G, Piatti S. Mad3/BubR1 phosphorylation during spindle checkpoint activation depends on both Polo and Aurora kinases in budding yeast. Cell Cycle. 2005;4: 972–980. doi: 10.4161/cc.4.7.1829 15970700

42. Mishra PK, Basrai MA. Protein kinases in mitotic phosphorylation of budding yeast CENP-A. Curr Genet. 2019;65: 1325–1332. doi: 10.1007/s00294-019-00997-5 31119371

43. Cherry JM, Hong EL, Amundsen C, Balakrishnan R, Binkley G, Chan ET, et al. Saccharomyces Genome Database: The genomics resource of budding yeast. Nucleic Acids Res. 2012;40: 700–705. doi: 10.1093/nar/gkr1029 22110037

44. Jakopec V, Topolski B, Fleig U. Sos7, an Essential Component of the Conserved Schizosaccharomyces pombe Ndc80-MIND-Spc7 Complex, Identifies a New Family of Fungal Kinetochore Proteins. Mol Cell Biol. 2012;32: 3308–3320. doi: 10.1128/MCB.00212-12 22711988

45. A Protein Interaction Map of the Mitotic Spindle. Mol Biol Cell. 2007;18: 3250–3263. doi: 10.1091/mbc.e07-04-0334 17567948

46. Wang Y, Zhang X, Zhang H, Lu Y, Huang H, Dong X, et al. Coiled-coil networking shapes cell molecular machinery. Mol Biol Cell. 2012;23: 3911–3922. doi: 10.1091/mbc.E12-05-0396 22875988

47. Mortensen EM, Haas W, Gygi M, Gygi SP, Kellogg DR. Cdc28-dependent regulation of the Cdc5/Polo kinase. Curr Biol. 2005;15: 2033–2037. doi: 10.1016/j.cub.2005.10.046 16303563

48. Elia AEH, Cantley LC, Yaffe MB. Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates. Science. 2003;299: 1228–1231. doi: 10.1126/science.1079079 12595692

49. Chen YC, Weinreich M. Dbf4 regulates the Cdc5 polo-like kinase through a distinct non-canonical binding interaction. J Biol Chem. 2010;285: 41244–41254. doi: 10.1074/jbc.M110.155242 21036905

50. Charles JF, Jaspersen SL, Tinker-Kulberg RL, Hwang L, Szidon A, Morgan DO. The polo-related kinase cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae. Curr Biol. 1998;8: 497–507. doi: 10.1016/s0960-9822(98)70201-5 9560342

51. Donaldson MM, Tavares ÁAM, Ohkura H, Deak P, Glover DM. Metaphase arrest with centromere separation in polo mutants of Drosophila. J Cell Biol. 2001;153: 663–675. doi: 10.1083/jcb.153.4.663 11352929

52. Wong OK, Fang G. Cdk1 phosphorylation of BubR1 controls spindle checkpoint arrest and Plk1-mediated formation of the 3F3/2 epitope. J Cell Biol. 2007;179: 611–617. doi: 10.1083/jcb.200708044 17998400

53. Liu D, Davydenko O, Lampson MA. Polo-like kinase-1 regulates kinetochore-microtubule dynamics and spindle checkpoint silencing. J Cell Biol. 2012;198: 491–499. doi: 10.1083/jcb.201205090 22908307

54. Conde C, Osswald M, Barbosa J, Moutinho-Santos T, Pinheiro D, Guimarães S, et al. Drosophila Polo regulates the spindle assembly checkpoint through Mps1-dependent BubR1 phosphorylation. EMBO J. 2013;32: 1761–1777. doi: 10.1038/emboj.2013.109 23685359

55. O’Connor A, Maffini S, Rainey MD, Kaczmarczyk A, Gaboriau D, Musacchio A, et al. Requirement for PLK1 kinase activity in the maintenance of a robust spindle assembly checkpoint. Biol Open. 2016;5: 11–19. doi: 10.1242/bio.014969 26685311

56. Espeut J, Lara-Gonzalez P, Sassine M, Shiau AK, Desai A, Abrieu A. Natural Loss of Mps1 Kinase in Nematodes Uncovers a Role for Polo-like Kinase 1 in Spindle Checkpoint Initiation. Cell Rep. 2015;12: 58–65. doi: 10.1016/j.celrep.2015.05.039 26119738

57. von Schubert C, Cubizolles F, Bracher JM, Sliedrecht T, Kops GJPL, Nigg EA. Plk1 and Mps1 Cooperatively Regulate the Spindle Assembly Checkpoint in Human Cells. Cell Rep. 2015;12: 66–78. doi: 10.1016/j.celrep.2015.06.007 26119734

58. Jia L, Li B, Yu H. The Bub1-Plk1 kinase complex promotes spindle checkpoint signalling through Cdc20 phosphorylation. Nat Commun. 2016;7: 10818. doi: 10.1038/ncomms10818 26912231

59. Buttrick GJ, Lancaster TC, Meadows JC, Millar JBA. Plo1 phosphorylates Dam1 to promote chromosome bi-orientation in fission yeast. J Cell Sci. 2012;125: 1645–1651. doi: 10.1242/jcs.096826 22375062

60. Yeong FM, Lim HH, Padmashree CG, Surana U. Exit from mitosis in budding yeast: Biphasic inactivation of the Cdc28-Clb2 mitotic kinase and the role of Cdc20. Mol Cell. 2000;5: 501–511. doi: 10.1016/s1097-2765(00)80444-x 10882135

61. Makrantoni V, Stark MJR. Efficient Chromosome Biorientation and the Tension Checkpoint in Saccharomyces cerevisiae both Require Bir1. Mol Cell Biol. 2009/06/17. 2009;29: 4552–4562. doi: 10.1128/MCB.01911-08 19528231

62. Kang YH, Park JE, Yu LR, Soung NK, Yun SM, Bang JK, et al. Self-Regulated Plk1 Recruitment to Kinetochores by the Plk1-PBIP1 Interaction Is Critical for Proper Chromosome Segregation. Mol Cell. 2006;24: 409–422. doi: 10.1016/j.molcel.2006.10.016 17081991

63. Kang YH, Park CH, Kim TS, Soung NK, Bang JK, Kim BY, et al. Mammalian polo-like kinase 1-dependent regulation of the PBIP1-CENP-Q complex at kinetochores. J Biol Chem. 2011;286: 19744–19757. doi: 10.1074/jbc.M111.224105 21454580

64. Park CH, Park JE, Kim TS, Kang YH, Soung NK, Zhou M, et al. Mammalian polo-like Kinase 1 (Plk1) promotes proper chromosome segregation by phosphorylating and delocalizing the PBIP1·CENP-Q complex from kinetochores. J Biol Chem. 2015;290: 8569–8581. doi: 10.1074/jbc.M114.623546 25670858

65. Hornung P, Troc P, Malvezzi F, Maier M, Demianova Z, Zimniak T, et al. A cooperative mechanism drives budding yeast kinetochore assembly downstream of CENP-A. J Cell Biol. 2014;206: 509–524. doi: 10.1083/jcb.201403081 25135934

66. Albuquerque CP, Smolka MB, Payne SH, Bafna V, Eng J, Zhou H. A multidimensional chromatography technology for in-depth phosphoproteome analysis. Mol Cell Proteomics. 2008;7: 1389–1396. doi: 10.1074/mcp.M700468-MCP200 18407956

67. Holt LJ, Tuch BB, Villen J, Johnson AD, Gygi SP, Morgan DO. Global Analysis of Cdk1 Substrate Phosphorylation Sites Provides Insights into Evolution. Science. 2009;325: 1682–1686. doi: 10.1126/science.1172867 19779198

68. Gnad F, De Godoy LMF, Cox J, Neuhauser N, Ren S, Olsen J V., et al. High-accuracy identification and bioinformatic analysis of in vivo protein phosphorylation sites in yeast. Proteomics. 2009;9: 4642–4652. doi: 10.1002/pmic.200900144 19795423

69. Breitkreutz A, Choi H, Sharom JR, Boucher L, Neduva V, Larsen B, et al. A global protein kinase and phosphatase interaction network in yeast. Science. 2010;328: 1043–1046. doi: 10.1126/science.1176495 20489023

70. Anedchenko EA, Samel-Pommerencke A, Tran Nguyen TM, Shahnejat-Bushehri S, Pöpsel J, Lauster D, et al. The kinetochore module Okp1 CENP-Q /Ame1 CENP-U is a reader for N-terminal modifications on the centromeric histone Cse4 CENP-A. EMBO J. 2019;38: e98991. doi: 10.15252/embj.201898991 30389668

71. Fischböck-Halwachs J, Singh S, Potocnjak M, Hagemann G, Solis-Mezarino V, Woike S, et al. The COMA complex interacts with Cse4 and positions Sli15/ipl1 at the budding yeast inner kinetochore. Elife. 2019;8: 1–28. doi: 10.7554/eLife.42879 31112132

72. Winzeler EA, Shoemaker DD, Astromoff A, Liang H, Anderson K, Andre B, et al. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science. 1999;285: 901–906. doi: 10.1126/science.285.5429.901 10436161

73. Li Z, Vizeacoumar FJ, Bahr S, Li J, Warringer J, Vizeacoumar FS, et al. Systematic exploration of essential yeast gene function with temperature-sensitive mutants. Nat Biotechnol. 2011;29: 361–367. doi: 10.1038/nbt.1832 21441928

74. Hartwell LH, Mortimer RK, Culotti J, Culotti M. Genetic control of the cell division cycle in yeast: V. Genetic analysis of cdc mutants. Genetics. 1973;74: 267–286. 17248617

75. Hartzog GA, Fu J. The Spt4-Spt5 complex: A multi-faceted regulator of transcription elongation. Biochim Biophys Acta—Gene Regul Mech. 2013;1829: 105–115. doi: 10.1016/j.bbagrm.2012.08.007 22982195

76. Basrai MA, Kingsbury J, Koshland D, Spencer F, Hieter P. Faithful chromosome transmission requires Spt4p, a putative regulator of chromatin structure in Saccharomyces cerevisiae. Mol Cell Biol. 1996;16: 2838–2847. doi: 10.1128/mcb.16.6.2838 8649393

77. Crotti LB, Basrai MA. Functional roles for evolutionarily conserved Spt4p at centromeres and heterochromatin in Saccharomyces cerevisiae. EMBO J. 2004;23: 1804–1814. doi: 10.1038/sj.emboj.7600161 15057281

78. Liu Y, Warfield L, Zhang C, Luo J, Allen J, Lang WH, et al. Phosphorylation of the Transcription Elongation Factor Spt5 by Yeast Bur1 Kinase Stimulates Recruitment of the PAF Complex. Mol Cell Biol. 2009;29: 4852–4863. doi: 10.1128/MCB.00609-09 19581288

79. Zhou K, Kuo WHW, Fillingham J, Greenblatt JF. Control of transcriptional elongation and cotranscriptional histone modification by the yeast BUR kinase substrate Spt5. Proc Natl Acad Sci U S A. 2009;106: 6956–6961. doi: 10.1073/pnas.0806302106 19365074

80. Murray S, Udupa R, Yao S, Hartzog G, Prelich G. Phosphorylation of the RNA Polymerase II Carboxy-Terminal Domain by the Bur1 Cyclin-Dependent Kinase. Mol Cell Biol. 2001;21: 4089–4096. doi: 10.1128/MCB.21.13.4089-4096.2001 11390638

81. Keogh M-C, Podolny V, Buratowski S. Bur1 Kinase Is Required for Efficient Transcription Elongation by RNA Polymerase II. Mol Cell Biol. 2003;23: 7005–7018. doi: 10.1128/mcb.23.19.7005-7018.2003 12972617

82. Chun Y, Joo YJ, Suh H, Batot G, Hill CP, Formosa T, et al. Selective Kinase Inhibition Shows That Bur1 (Cdk9) Phosphorylates the Rpb1 Linker In Vivo. Mol Cell Biol. 2019;39. doi: 10.1128/mcb.00602-18 31085683

83. Tsuchiya E, Hosotani T, Miyakawa T. A mutation in NPS1/STH1, an essential gene encoding a component of a novel chromatin-remodeling complex RSC, alters the chromatin structure of Saccharomyces cerevisiae centromeres. Nucleic Acids Res. 1998;26: 3286–3292. doi: 10.1093/nar/26.13.3286 9628931

84. Spain MM, Ansari SA, Pathak R, Palumbo MJ, Morse RH, Govind CK. The RSC Complex Localizes to Coding Sequences to Regulate Pol II and Histone Occupancy. Mol Cell. 2014;56: 653–666. doi: 10.1016/j.molcel.2014.10.002 25457164

85. Hsu J, Huang J, Meluh PB, Laurent BC. The Yeast RSC Chromatin-Remodeling Complex Is Required for Kinetochore Function in Chromosome Segregation. Mol Cell Biol. 2003;23: 3202–3215. doi: 10.1128/mcb.23.9.3202-3215.2003 12697820

86. Baetz KK, Krogan NJ, Emili A, Greenblatt J, Hieter P. The ctf13-30/CTF13 Genomic Haploinsufficiency Modifier Screen Identifies the Yeast Chromatin Remodeling Complex RSC, Which Is Required for the Establishment of Sister Chromatid Cohesion. Mol Cell Biol. 2004;24: 1232–1244. doi: 10.1128/mcb.24.3.1232-1244.2003 14729968

87. Ocampo J, Chereji R V., Eriksson PR, Clark DJ. Contrasting roles of the RSC and ISW1/CHD1 chromatin remodelers in RNA polymerase II elongation and termination. Genome Res. 2019;29: 407–417. doi: 10.1101/gr.242032.118 30683752

88. Herrero E, Thorpe PH. Synergistic Control of Kinetochore Protein Levels by Psh1 and Ubr2. PLoS Genet. 2016;12: 1–23. doi: 10.1371/journal.pgen.1005855 26891228

89. Sopko R, Huang D, Preston N, Chua G, Papp B, Kafadar K, et al. Mapping pathways and phenotypes by systematic gene overexpression. Mol Cell. 2006;21: 319–330. doi: 10.1016/j.molcel.2005.12.011 16455487

90. Yoshikawa K, Tanaka T, Ida Y, Furusawa C, Hirasawa T, Shimizu H. Comprehensive phenotypic analysis of single-gene deletion and overexpression strains of Saccharomyces cerevisiae. Yeast. 2011;28: 349–361. doi: 10.1002/yea.1843 21341307

91. Liu CR, Chang CR, Chern Y, Wang TH, Hsieh WC, Shen WC, et al. Spt4 is selectively required for transcription of extended trinucleotide repeats. Cell. 2012;148: 690–701. doi: 10.1016/j.cell.2011.12.032 22341442

92. Ling YH, Yuen KWY. Point centromere activity requires an optimal level of centromeric noncoding RNA. Proc Natl Acad Sci U S A. 2019;116: 6270–6279. doi: 10.1073/pnas.1821384116 30850541

93. Chen CF, Pohl TJ, Chan A, Slocum JS, Zakian VA. Saccharomyces cerevisiae centromere RNA is negatively regulated by Cbf1 and its unscheduled synthesis impacts CenH3 binding. Genetics. 2019;213: 465–479. doi: 10.1534/genetics.119.302528 31391265

94. Baker RE, Harris R, Zhang K. Mutations synthetically lethal with cep1 target S. cerevisiae kinetochore components. Genetics. 1998;149: 73–85. Available: http://www.ncbi.nlm.nih.gov/pubmed/9584087 9584087

95. Hartzog GA, Wada T, Handa H, Winston F. Evidence that Spt4, Spt5, and Spt6 control transcription elongation by RNA polymerase II in Saccharomyces cerevisiae. Genes Dev. 1998;12: 357–369. doi: 10.1101/gad.12.3.357 9450930

96. Gaur NA, Hasek J, Brickner DG, Qiu H, Zhang F, Wong CM, et al. Vps factors are required for efficient transcription elongation in budding yeast. Genetics. 2013;193: 829–851. doi: 10.1534/genetics.112.146308 23335340

97. Desmoucelles C, Pinson B, Saint-Marc C, Daignan-Fornier B. Screening the yeast “Disruptome” for mutants affecting resistance to the immunosuppressive drug, mycophenolic acid. J Biol Chem. 2002;277: 27036–27044. doi: 10.1074/jbc.M111433200 12016207

98. McKinley KL, Cheeseman IM. Polo-like kinase 1 licenses CENP-a deposition at centromeres. Cell. 2014;158: 397–411. doi: 10.1016/j.cell.2014.06.016 25036634

99. Swartz SZ, McKay LS, Su KC, Bury L, Padeganeh A, Maddox PS, et al. Quiescent Cells Actively Replenish CENP-A Nucleosomes to Maintain Centromere Identity and Proliferative Potential. Dev Cell. 2019;51: 35–48.e7. doi: 10.1016/j.devcel.2019.07.016 31422918

100. Bobkov GOM, Gilbert N, Heun P. Centromere transcription allows CENP-A to transit from chromatin association to stable incorporation. J Cell Biol. 2018;217: 1957–1972. doi: 10.1083/jcb.201611087 29626011

101. Zhu J, Cheng KCL, Yuen KWY. Histone H3K9 and H4 Acetylations and Transcription Facilitate the Initial CENP-AHCP-3 Deposition and de Novo Centromere Establishment in Caenorhabditis elegans Artificial Chromosomes. Epigenetics and Chromatin. 2018;11: 1–20. doi: 10.1186/s13072-017-0171-z 29310712

102. 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: 3924–3936.e4. doi: 10.1016/j.cub.2018.10.049 30503616

103. Catania S, Pidoux AL, Allshire RC. Sequence Features and Transcriptional Stalling within Centromere DNA Promote Establishment of CENP-A Chromatin. van Steensel B, editor. PLoS Genet. 2015;11: e1004986. doi: 10.1371/journal.pgen.1004986 25738810

104. Perea-Resa C, Blower MD. Centromere Biology: Transcription Goes on Stage. Mol Cell Biol. 2018;38: MCB.00263–18. doi: 10.1128/mcb.00263-18 29941491

105. Smurova K, De Wulf P. Centromere and Pericentromere Transcription: Roles and Regulation … in Sickness and in Health. Front Genet. 2018;9: 1–26. doi: 10.3389/fgene.2018.00001 29387083

106. Hill A, Bloom K. Genetic manipulation of centromere function. Mol Cell Biol. 1987;7: 2397–2405. doi: 10.1128/mcb.7.7.2397 3302676

107. Reid RJD, Sunjevaric I, Voth WP, Ciccone S, Du W, Olsen AE, et al. Chromosome-scale genetic mapping using a set of 16 conditionally stable Saccharomyces cerevisiae chromosomes. Genetics. 2008;180: 1799–1808. doi: 10.1534/genetics.108.087999 18832360

108. Reid RJD, González-Barrera S, Sunjevaric I, Alvaro D, Ciccone S, Wagner M, et al. Selective ploidy ablation, a high-throughput plasmid transfer protocol, identifies new genes affecting topoisomerase I-induced DNA damage. Genome Res. 2010/12/22. 2011;21: 477–486. doi: 10.1101/gr.109033.110 21173034

109. Rossio V, Galati E, Ferrari M, Pellicioli A, Sutani T, Shirahige K, et al. The RSC chromatin-remodeling complex influences mitotic exit and adaptation to the spindle assembly checkpoint by controlling the Cdc14 phosphatase. J Cell Biol. 2010;191: 981–997. doi: 10.1083/jcb.201007025 21098112

110. Chiroli E, Rancati G, Catusi I, Lucchini G, Piatti S. Cdc14 inhibition by the spindle assembly checkpoint prevents unscheduled centrosome separation in budding yeast. Mol Biol Cell. 2009;20: 2626–2637. doi: 10.1091/mbc.e08-11-1150 19339280

111. Rawal CC, Riccardo S, Pesenti C, Ferrari M, Marini F, Pellicioli A. Reduced kinase activity of polo kinase Cdc5 affects chromosome stability and DNA damage response in S. cerevisiae. Cell Cycle. 2016;15: 2906–2919. doi: 10.1080/15384101.2016.1222338 27565373

112. Bader JR, Kasuboski JM, Winding M, Vaughan PS, Hinchcliffe EH, Vaughan KT. Polo-like kinase1 is required for recruitment of dynein to kinetochores during mitosis. J Biol Chem. 2011;286: 20769–20777. doi: 10.1074/jbc.M111.226605 21507953

113. Yeh TY, Kowalska AK, Scipioni BR, Cheong FKY, Zheng M, Derewenda U, et al. Dynactin helps target Polo-like kinase 1 to kinetochores via its left-handed beta-helical p27 subunit. EMBO J. 2013;32: 1023–1035. doi: 10.1038/emboj.2013.30 23455152

114. Nakano M, Cardinale S, Noskov VN, Gassmann R, Vagnarelli P, Kandels-Lewis S, et al. Inactivation of a Human Kinetochore by Specific Targeting of Chromatin Modifiers. Dev Cell. 2008;14: 507–522. doi: 10.1016/j.devcel.2008.02.001 18410728

115. Cardinale S, Bergmann JH, Kelly D, Nakano M, Valdivia MM, Kimura H, et al. Hierarchical inactivation of a synthetic human kinetochore by a chromatin modifier. Zheng Y, editor. Mol Biol Cell. 2009;20: 4194–4204. doi: 10.1091/mbc.e09-06-0489 19656847

116. Edmondson DG, Smith MM, Roth SY. Repression domain of the yeast global repressor Tup1 interacts directly with histones H3 and H4. Genes Dev. 1996;10: 1247–1259. doi: 10.1101/gad.10.10.1247 8675011

117. Watson AD, Edmondson DG, Bone JR, Mukai Y, Yu Y, Du W, et al. Ssn6-Tup1 interacts with class I histone deacetylases required for repression. Genes Dev. 2000;14: 2737–2744. doi: 10.1101/gad.829100 11069890

118. Wu J, Suka N, Carlson M, Grunstein M. TUP1 utilizes histone H3/H2B-specific HDA1 deacetylase to repress gene activity in yeast. Mol Cell. 2001;7: 117–126. doi: 10.1016/s1097-2765(01)00160-5 11172717

119. Fleming AB, Beggs S, Church M, Tsukihashi Y, Pennings S. The yeast Cyc8-Tup1 complex cooperates with Hda1p and Rpd3p histone deacetylases to robustly repress transcription of the subtelomeric FLO1 gene. Biochim Biophys Acta—Gene Regul Mech. 2014;1839: 1242–1255. doi: 10.1016/j.bbagrm.2014.07.022 25106892

120. Kliewe F, Engelhardt M, Aref R, Schüller HJ. Promoter recruitment of corepressors Sin3 and Cyc8 by activator proteins of the yeast Saccharomyces cerevisiae. Curr Genet. 2017;63: 739–750. doi: 10.1007/s00294-017-0677-8 28175933

121. Papamichos-Chronakis M, Petrakis T, Ktistaki E, Topalidou I, Tzamarias D. Cti6 a PHD domain protein bridges the Cyc8-Tup1 corepressor and the SAGA coactivator to overcome repression at GAL1. Mol Cell. 2002;9: 1297–1305. doi: 10.1016/s1097-2765(02)00545-2 12086626

122. Proft M, Struhl K. Hog1 kinase converts the Sko1-Cyc8-Tup1 repressor complex into an activator that recruits SAGA and SWI/SNF in response to osmotic stress. Mol Cell. 2002;9: 1307–1317. doi: 10.1016/s1097-2765(02)00557-9 12086627

123. Mellor J, Jiang W, Funk M, Rathjen J, Barnes CA, Hinz T, et al. CPF1, a yeast protein which functions in centromeres and promoters. EMBO J. 1990;9: 4017–4026. doi: 10.1002/j.1460-2075.1990.tb07623.x 2249662

124. Ohkuni K, Kitagawa K. Endogenous transcription at the centromere facilitates centromere activity in budding yeast. Curr Biol. 2011;21: 1695–1703. doi: 10.1016/j.cub.2011.08.056 22000103

125. Moreau JL, Lee M, Mahachi N, Vary J, Mellor J, Tsukiyama T, et al. Regulated displacement of TBP from the PHO8 promoter in vivo requires Cbf1 and the Isw1 chromatin remodeling complex. Mol Cell. 2003;11: 1609–1620. doi: 10.1016/s1097-2765(03)00184-9 12820973

126. Smolka MB, Albuquerque CP, Chen SH, Zhou H. Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. Proc Natl Acad Sci U S A. 2007;104: 10364–10369. doi: 10.1073/pnas.0701622104 17563356

127. Chen SH, Albuquerque CP, Liang J, Suhandynata RT, Zhou H. A proteome-wide analysis of kinase-substrate network in the DNA damage response. J Biol Chem. 2010;285: 12803–12812. doi: 10.1074/jbc.M110.106989 20190278

128. Bodenmiller B, Wanka S, Kraft C, Urban J, Campbell D, Pedrioli PG, et al. Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast. Sci Signal. 2010;3: rs4. doi: 10.1126/scisignal.2001182 21177495

129. Beltrao P, Albanèse V, Kenner LR, Swaney DL, Burlingame A, Villén J, et al. Systematic functional prioritization of protein posttranslational modifications. Cell. 2012;150: 413–425. doi: 10.1016/j.cell.2012.05.036 22817900

130. Swaney DL, Beltrao P, Starita L, Guo A, Rush J, Fields S, et al. Global analysis of phosphorylation and ubiquitylation cross-talk in protein degradation. Nat Methods. 2013;10: 676–682. doi: 10.1038/nmeth.2519 23749301

131. Chen CF, Pohl TJ, Pott S, Zakian VA. Two Pif1 family DNA helicases cooperate in centromere replication and segregation in Saccharomyces cerevisiae. Genetics. 2019;211: 105–119. doi: 10.1534/genetics.118.301710 30442759

132. Dronamraju R, Kerschner JL, Peck SA, Hepperla AJ, Adams AT, Hughes KD, et al. Casein Kinase II Phosphorylation of Spt6 Enforces Transcriptional Fidelity by Maintaining Spn1-Spt6 Interaction. Cell Rep. 2018;25: 3476–3489.e5. doi: 10.1016/j.celrep.2018.11.089 30566871

133. Bobkov GOM, Huang A, van den Berg SJW, Mitra S, Anselm E, Lazou V, et al. Spt6 is a maintenance factor for centromeric CENP-A. Nat Commun. 2020;11: 2919. doi: 10.1038/s41467-020-16695-7 32522980

134. Lidschreiber M, Leike K, Cramer P. Cap Completion and C-Terminal Repeat Domain Kinase Recruitment Underlie the Initiation-Elongation Transition of RNA Polymerase II. Mol Cell Biol. 2013;33: 3805–3816. doi: 10.1128/MCB.00361-13 23878398

135. Mayekar MK, Gardner RG, Arndt KM. The Recruitment of the Saccharomyces cerevisiae Paf1 Complex to Active Genes Requires a Domain of Rtf1 That Directly Interacts with the Spt4-Spt5 Complex. Mol Cell Biol. 2013;33: 3259–3273. doi: 10.1128/MCB.00270-13 23775116

136. Dronamraju R, Strahl BD. A feed forward circuit comprising Spt6, Ctk1 and PAF regulates Pol II CTD phosphorylation and transcription elongation. Nucleic Acids Res. 2014;42: 870–881. doi: 10.1093/nar/gkt1003 24163256

137. Battaglia S, Lidschreiber M, Baejen C, Torkler P, Vos SM, Cramer P. RNA-dependent chromatin association of transcription elongation factors and pol II CTD kinases. Elife. 2017;6: 1–26. doi: 10.7554/eLife.25637 28537551

138. Latham JA, Chosed RJ, Wang S, Dent SYR. Chromatin signaling to kinetochores: Transregulation of Dam1 methylation by histone H2B ubiquitination. Cell. 2011;146: 709–719. doi: 10.1016/j.cell.2011.07.025 21884933

139. Burugula BB, Jeronimo C, Pathak R, Jones JW, Robert F, Govind CK. Histone Deacetylases and Phosphorylated Polymerase II C-Terminal Domain Recruit Spt6 for Cotranscriptional Histone Reassembly. Mol Cell Biol. 2014;34: 4115–4129. doi: 10.1128/MCB.00695-14 25182531

140. Lee J, Shik Choi E, David Seo H, Kang K, Gilmore JM, Florens L, et al. Chromatin remodeller Fun30Fft3 induces nucleosome disassembly to facilitate RNA polymerase II elongation. Nat Commun. 2017;8: 14527. doi: 10.1038/ncomms14527 28218250

141. Durand-Dubief M, Will WR, Petrini E, Theodorou D, Harris RR, Crawford MR, et al. SWI/SNF-Like Chromatin Remodeling Factor Fun30 Supports Point Centromere Function in S. cerevisiae. PLoS Genet. 2012;8: 15–21. doi: 10.1371/journal.pgen.1002974 23028372

142. Darieva Z, Bulmer R, Pic-Taylor A, Doris KS, Geymonat M, Sedgwick SG, et al. Polo kinase controls cell-cycle-dependent transcription by targeting a coactivator protein. Nature. 2006;444: 494–498. doi: 10.1038/nature05339 17122856

143. Fu Z, Malureanu L, Huang J, Wang W, Li H, van Deursen JM, et al. Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression. Nat Cell Biol. 2008;10: 1076–1082. doi: 10.1038/ncb1767 19160488

144. Stanlie A, Begum NA, Akiyama H, Honjo T. The DSIF subunits Spt4 and Spt5 have distinct roles at various phases of immunoglobulin class switch recombination. PLoS Genet. 2012;8. doi: 10.1371/journal.pgen.1002675 22570620

145. Lindstrom DL, Squazzo SL, Muster N, Burckin TA, Wachter KC, Emigh CA, et al. Dual Roles for Spt5 in Pre-mRNA Processing and Transcription Elongation Revealed by Identification of Spt5-Associated Proteins. Mol Cell Biol. 2003;23: 1368–1378. doi: 10.1128/mcb.23.4.1368-1378.2003 12556496

146. Silva A, Cavero S, Sarah V, Solé C, Böttcher R, Chávez S, et al. Regulation of transcription elongation in response to osmostress. Churchman S, editor. PLoS Genet. 2017;13: e1007090. doi: 10.1371/journal.pgen.1007090 29155810

147. Gray CH, Good VM, Tonks NK, Barford D. The structure of the cell cycle protein Cdc14 reveals a proline-directed protein phosphatase. EMBO J. 2003;22: 3524–3535. doi: 10.1093/emboj/cdg348 12853468

148. Bremmer SC, Hall H, Martinez JS, Eissler CL, Hinrichsen TH, Rossie S, et al. Cdc14 phosphatases preferentially dephosphorylate a subset of cyclin-dependent kinase (Cdk) sites containing phosphoserine. J Biol Chem. 2012;287: 1662–1669. doi: 10.1074/jbc.M111.281105 22117071

149. Touati SA, Hofbauer L, Jones AW, Snijders AP, Kelly G, Uhlmann F. Cdc14 and PP2A Phosphatases Cooperate to Shape Phosphoproteome Dynamics during Mitotic Exit. Cell Rep. 2019;29: 2105–2119.e4. doi: 10.1016/j.celrep.2019.10.041 31722221

150. Akiyoshi B, Biggins S. Cdc14-dependent dephosphorylation of a kinetochore protein prior to anaphase in Saccharomyces cerevisiae. Genetics. 2010;186: 1487–1491. doi: 10.1534/genetics.110.123653 20923974

151. Botchkarev V V., Garabedian M V., Lemos B, Paulissen E, Haber JE. The budding yeast Polo-like kinase localizes to distinct populations at centrosomes during mitosis. Mol Biol Cell. 2017;28: 1011–1020. doi: 10.1091/mbc.E16-05-0324 28228549

152. Clemente-Blanco A, Sen N, Mayan-Santos M, Sacristén MP, Graham B, Jarmuz A, et al. Cdc14 phosphatase promotes segregation of telomeres through repression of RNA polymerase II transcription. Nat Cell Biol. 2011;13: 1450–1456. doi: 10.1038/ncb2365 22020438

153. Guillamot M, Manchado E, Chiesa M, Gṕmez-López G, Pisano DG, Sacristán MP, et al. Cdc14b regulates mammalian RNA polymerase II and represses cell cycle transcription. Sci Rep. 2011;1: 1–7. doi: 10.1038/srep00001 22355520

154. Clemente-Blanco A, Mayán-Santos M, Schneider DA, Machín F, Jarmuz A, Tschochner H, et al. Cdc14 inhibits transcription by RNA polymerase I during anaphase. Nature. 2009;458: 219–222. doi: 10.1038/nature07652 19158678

155. Dittmar JC, Reid RJD, Rothstein R. ScreenMill: A freely available software suite for growth measurement, analysis and visualization of high-throughput screen data. BMC Bioinformatics. 2010/06/30. 2010;11: 353. doi: 10.1186/1471-2105-11-353 20584323

156. Ledesma-Fernández E, Thorpe PH. Fluorescent foci quantitation for high-throughput analysis. J Biol Methods. 2015;2: 22. doi: 10.14440/jbm.2015.62 26290880

157. Eisen MB, Spellman PT, Brown PO, Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998;95: 14863–14868. doi: 10.1073/pnas.95.25.14863 9843981

158. Saldanha AJ. Java Treeview—Extensible visualization of microarray data. Bioinformatics. 2004;20: 3246–3248. doi: 10.1093/bioinformatics/bth349 15180930

159. Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z. GOrilla: A tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics. 2009;10: 48. doi: 10.1186/1471-2105-10-48 19192299

160. Haase SB, Reed SI. Improved flow cytometric analysis of the budding yeast cell cycle. Cell Cycle. 2002;1: 117–121. doi: 10.4161/cc.1.2.114 12429918

161. Rosebrock AP. Analysis of the budding yeast cell cycle by flow cytometry. Cold Spring Harb Protoc. 2017;2017: 63–68. doi: 10.1101/pdb.prot088740 28049776

Článek vyšel v časopise

PLOS Genetics

2020 Číslo 8

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…

Kurzy Doporučená témata Časopisy
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

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


Nemáte účet?  Registrujte se

VIRTUÁLNÍ ČEKÁRNA ČR Jste praktický lékař nebo pediatr? Zapojte se! Jste praktik nebo pediatr? Zapojte se!