title: The nucleolus—guardian of cellular homeostasis and genome integrity.
abstract: All organisms sense and respond to conditions that stress their homeostasis by downregulating the synthesis of rRNA and ribosome biogenesis, thus designating the nucleolus as the central hub in coordinating the cellular stress response. One of the most intriguing roles of the nucleolus, long regarded as a mere ribosome-producing factory, is its participation in monitoring cellular stress signals and transmitting them to the RNA polymerase I (Pol I) transcription machinery. As rRNA synthesis is a most energy-consuming process, switching off transcription of rRNA genes is an effective way of saving the energy required to maintain cellular homeostasis during acute stress. The Pol I transcription machinery is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production which, in turn, guides cell growth and proliferation. This review focuses on the mechanisms that link cell physiology to rDNA silencing, a prerequisite for nucleolar integrity and cell survival.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Grummt
mesh_terms: D000818:Animals; D002466:Cell Nucleolus / Q000235:genetics* / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D042822:Genomic Instability; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D014176:Protein Biosynthesis; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D014158:Transcription, Genetic
chemical_list: D004275:DNA, Ribosomal; D012335:RNA, Ribosomal; D012318:RNA Polymerase I
references.citation: FEBS J. 2010 Nov;277(22):4626-39
references.pmid: 20977666
references.citation: BMC Cell Biol. 2011 Aug 11;12:33
references.pmid: 21835027
references.citation: Curr Opin Cell Biol. 2008 Jun;20(3):303-9
references.pmid: 18468877
references.citation: Cell Mol Life Sci. 2007 Jan;64(1):29-49
references.pmid: 17171232
references.citation: Curr Opin Genet Dev. 2000 Feb;10(1):94-9
references.pmid: 10679383
references.citation: EMBO J. 2002 Sep 2;21(17):4632-40
references.pmid: 12198165
references.citation: Mol Cell Biol. 1985 Jun;5(6):1358-69
references.pmid: 3929071
references.citation: EMBO J. 2007 Feb 21;26(4):944-54
references.pmid: 17268553
references.citation: Bioessays. 2008 Mar;30(3):267-72
references.pmid: 18293366
references.citation: EMBO J. 2007 Mar 21;26(6):1560-8
references.pmid: 17318177
references.citation: Trends Pharmacol Sci. 2010 May;31(5):212-20
references.pmid: 20226541
references.citation: Annu Rev Cell Dev Biol. 2008;24:131-57
references.pmid: 18616426
references.citation: Mol Cell Proteomics. 2010 Jan;9(1):117-30
references.pmid: 19812395
references.citation: Science. 2011 Feb 4;331(6017):593-6
references.pmid: 21233348
references.citation: Nature. 2012 Jul 5;487(7405):114-8
references.pmid: 22722849
references.citation: EMBO J. 1996 May 1;15(9):2217-26
references.pmid: 8641287
references.citation: Lancet. 1995 Oct 14;346(8981):1009-11
references.pmid: 7475551
references.citation: Hepatology. 2013 Mar;57(3):1055-67
references.pmid: 23079745
references.citation: Biochim Biophys Acta. 2013 Mar-Apr;1829(3-4):393-404
references.pmid: 23063748
references.citation: Mol Cell. 2010 Oct 22;40(2):216-27
references.pmid: 20965417
references.citation: Science. 2002 Nov 22;298(5598):1623-6
references.pmid: 12446911
references.citation: Mol Cell. 2005 Jul 1;19(1):77-87
references.pmid: 15989966
references.citation: Chromosoma. 1997 Jun;105(7-8):470-80
references.pmid: 9211975
references.citation: Trends Cell Biol. 2007 Jun;17(6):292-301
references.pmid: 17475497
references.citation: Science. 2005 Sep 2;309(5740):1581-4
references.pmid: 16141077
references.citation: Mol Cell. 2012 Jan 27;45(2):147-57
references.pmid: 22284675
references.citation: Annu Rev Pathol. 2010;5:253-95
references.pmid: 20078221
references.citation: Sci STKE. 2004 Mar 09;2004(224):pe10
references.pmid: 15026578
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17781-6
references.pmid: 19815529
references.citation: Cancer Cell. 2004 May;5(5):465-75
references.pmid: 15144954
references.citation: Proteomics. 2010 Nov;10(22):4087-97
references.pmid: 21080495
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D181-4
references.pmid: 18984612
references.citation: Nat Cell Biol. 2007 Jan;9(1):25-35
references.pmid: 17159999
references.citation: Cell Cycle. 2005 Aug;4(8):1036-8
references.pmid: 16205120
references.citation: Biochem Soc Symp. 2006;(73):203-16
references.pmid: 16626300
references.citation: EMBO Rep. 2013 Aug;14(8):704-10
references.pmid: 23797874
references.citation: Nat Genet. 2002 Nov;32(3):393-6
references.pmid: 12368916
references.citation: Cancer Cell. 2012 Jul 10;22(1):51-65
references.pmid: 22789538
references.citation: Nature. 1990 Apr 26;344(6269):830-6
references.pmid: 2330041
references.citation: Curr Opin Cell Biol. 1999 Jun;11(3):385-90
references.pmid: 10395554
references.citation: EMBO J. 1995 Nov 1;14(21):5338-49
references.pmid: 7489723
references.citation: Circ Res. 2008 Mar 28;102(6):703-10
references.pmid: 18239138
references.citation: EMBO J. 2003 Nov 17;22(22):6068-77
references.pmid: 14609953
references.citation: PLoS Genet. 2009 Mar;5(3):e1000435
references.pmid: 19325889
references.citation: EMBO J. 2001 Sep 3;20(17):4892-900
references.pmid: 11532953
references.citation: Exp Cell Res. 1994 Mar;211(1):36-41
references.pmid: 7510250
references.citation: J Cell Biol. 2005 Aug 29;170(5):733-44
references.pmid: 16129783
references.citation: Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1733-8
references.pmid: 9050847
references.citation: Genes Dev. 2003 Jul 15;17(14):1691-702
references.pmid: 12865296
references.citation: Cell. 1992 Mar 6;68(5):965-76
references.pmid: 1547496
references.citation: Proteomics. 2010 Nov;10(22):4077-86
references.pmid: 20661956
references.citation: Nat Rev Mol Cell Biol. 2012 Mar 07;13(4):225-238
references.pmid: 22395773
references.citation: Genes Dev. 2006 May 1;20(9):1075-80
references.pmid: 16618798
references.citation: Annu Rev Pharmacol Toxicol. 2010;50:131-56
references.pmid: 20055700
references.citation: Trends Biochem Sci. 2005 Feb;30(2):87-96
references.pmid: 15691654
references.citation: Trends Biochem Sci. 2010 Jul;35(7):361-7
references.pmid: 20363631
references.citation: Proc Natl Acad Sci U S A. 1986 Feb;83(3):604-8
references.pmid: 3456157
references.citation: Mol Biol Cell. 2002 Nov;13(11):4100-9
references.pmid: 12429849
references.citation: Mol Cell Biol. 2003 Dec;23(23):8902-12
references.pmid: 14612427
references.citation: Genes Dev. 2005 Apr 15;19(8):933-41
references.pmid: 15805466
references.citation: J Biol Chem. 1996 Dec 13;271(50):31929-36
references.pmid: 8943238
references.citation: J Cell Sci. 2009 Feb 15;122(Pt 4):489-98
references.pmid: 19174463
references.citation: Science. 1994 Dec 23;266(5193):2015-8
references.pmid: 7801130
references.citation: Mol Cell Biol. 2005 Apr;25(7):2539-46
references.pmid: 15767661
references.citation: Cell. 2008 May 16;133(4):627-39
references.pmid: 18485871
references.citation: Cell. 1976 Mar;7(3):447-53
references.pmid: 947552
references.citation: Cell. 2000 Oct 13;103(2):239-52
references.pmid: 11057897
references.citation: Curr Opin Genet Dev. 2008 Apr;18(2):204-11
references.pmid: 18372168
references.citation: Mol Cell Proteomics. 2012 May;11(5):60-76
references.pmid: 22586326
references.citation: Nature. 2007 Nov 15;450(7168):440-4
references.pmid: 18004385
references.citation: EMBO J. 2001 Mar 15;20(6):1353-62
references.pmid: 11250901
references.citation: Genes Dev. 2004 Feb 15;18(4):423-34
references.pmid: 15004009
references.citation: Nature. 2005 Jan 6;433(7021):77-83
references.pmid: 15635413