title: The G4 genome.
abstract: Recent experiments provide fascinating examples of how G4 DNA and G4 RNA structures--aka quadruplexes--may contribute to normal biology and to genomic pathologies. Quadruplexes are transient and therefore difficult to identify directly in living cells, which initially caused skepticism regarding not only their biological relevance but even their existence. There is now compelling evidence for functions of some G4 motifs and the corresponding quadruplexes in essential processes, including initiation of DNA replication, telomere maintenance, regulated recombination in immune evasion and the immune response, control of gene expression, and genetic and epigenetic instability. Recognition and resolution of quadruplex structures is therefore an essential component of genome biology. We propose that G4 motifs and structures that participate in key processes compose the G4 genome, analogous to the transcriptome, proteome, or metabolome. This is a new view of the genome, which sees DNA as not only a simple alphabet but also a more complex geography. The challenge for the future is to systematically identify the G4 motifs that form quadruplexes in living cells and the features that confer on specific G4 motifs the ability to function as structural elements.
authors: Department of Immunology, University of Washington, Seattle, Washington, United States of America. maizels@u.washington.edu
authors: Nancy
authors: N
authors: Maizels
authors: Lucas T
authors: LT
authors: Gray
mesh_terms: D004247:DNA / Q000737:chemistry; D004265:DNA Helicases / Q000235:genetics; D004261:DNA Replication; D054856:G-Quadruplexes; D006801:Humans
chemical_list: D004247:DNA; D004265:DNA Helicases
references: Cell. 2010 Oct 29;143(3):367-78
references: 21029860
references: PLoS Pathog. 2013 Jan;9(1):e1003074
references: 23349628
references: Nat Rev Drug Discov. 2011 Apr;10(4):261-75
references: 21455236
references: Nat Chem. 2013 Mar;5(3):182-6
references: 23422559
references: Annu Rev Pathol. 2012;7:219-45
references: 22017584
references: Structure. 2010 Jan 13;18(1):73-82
references: 20152154
references: Genes Dev. 2004 Jul 1;18(13):1618-29
references: 15231739
references: Mol Cell. 2012 Mar 30;45(6):814-25
references: 22387027
references: Nucleic Acids Res. 2012 Jun;40(11):4727-41
references: 22351747
references: Neuron. 2011 Oct 20;72(2):257-68
references: 21944779
references: Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14579-84
references: 20679250
references: Oncogene. 2005 Sep 1;24(38):5791-8
references: 15940261
references: Mol Biosyst. 2010 Dec;6(12):2439-47
references: 20877913
references: EMBO J. 2011 Oct 05;30(19):3878-9
references: 21975374
references: J Biol Chem. 1998 Oct 16;273(42):27587-92
references: 9765292
references: Nature. 2007 Jun 21;447(7147):932-40
references: 17581576
references: Cell. 2011 May 27;145(5):678-91
references: 21620135
references: J Biol Chem. 2008 Dec 26;283(52):36132-9
references: 18978354
references: Science. 2009 Aug 7;325(5941):764-7
references: 19661435
references: J Virol. 2009 Oct;83(20):10336-46
references: 19656898
references: Nat Struct Mol Biol. 2012 Aug;19(8):837-44
references: 22751019
references: Cell. 2004 Jun 25;117(7):873-86
references: 15210109
references: Nucleic Acids Res. 2009 Nov;37(20):6784-98
references: 19759215
references: Nucleic Acids Res. 2011 Mar;39(5):1647-55
references: 21097466
references: Mol Cell. 2009 Aug 28;35(4):403-13
references: 19716786
references: Neurology. 2007 Aug 21;69(8):730-8
references: 17709704
references: Mol Cell Biol. 2008 Jun;28(12):4116-28
references: 18426915
references: Mol Cell. 2011 Jun 24;42(6):794-805
references: 21700224
references: Proc Natl Acad Sci U S A. 1996 May 28;93(11):5610-4
references: 8643624
references: Science. 2012 May 4;336(6081):593-7
references: 22556254
references: Nature. 1988 Jul 28;334(6180):364-6
references: 3393228
references: Nat Struct Mol Biol. 2011 Apr;18(4):478-85
references: 21399640
references: Nucleic Acids Res. 2012 Feb;40(4):1499-508
references: 22021377
references: Nat Struct Mol Biol. 2006 Dec;13(12):1055-9
references: 17146462
references: Nucleic Acids Res. 2012 Aug;40(15):7358-67
references: 22576367
references: Nucleic Acids Res. 2011 Jul;39(12):4975-83
references: 21371997
references: Nat Rev Genet. 2012 Feb 14;13(3):204-14
references: 22330764
references: Nucleic Acids Res. 2006;34(14):3887-96
references: 16914419
references: Curr Opin Struct Biol. 2006 Jun;16(3):288-98
references: 16714104
references: Genes Dev. 2005 Sep 15;19(18):2100-10
references: 16166375
references: Neuron. 2011 Oct 20;72(2):245-56
references: 21944778
references: Mol Cell. 2010 Dec 10;40(5):703-13
references: 21145480
references: Science. 2004 Dec 10;306(5703):1951-3
references: 15591207
references: J Am Chem Soc. 2012 Jul 25;134(29):11974-6
references: 22780456
references: Nature. 1991 May 23;351(6324):331-2
references: 1709723
references: Cell. 2009 Jul 10;138(1):90-103
references: 19596237
references: Nat Struct Mol Biol. 2011 Jul 03;18(8):950-5
references: 21725294
references: J Am Chem Soc. 2006 Dec 6;128(48):15461-8
references: 17132013
references: Mol Cell. 2012 Apr 27;46(2):115-24
references: 22541554
references: EMBO J. 2011 Aug 26;30(19):4033-46
references: 21873979
references: Curr Biol. 2005 Mar 8;15(5):470-4
references: 15753043
references: Nucleic Acids Res. 2010 Jul;38(13):4337-48
references: 20223771
references: Genome Res. 2010 Mar;20(3):351-60
references: 20110566
references: Cell. 2012 May 11;149(4):795-806
references: 22579284
references: Cancer Res. 2007 Mar 15;67(6):2586-94
references: 17363577
references: Nature. 2002 Jun 20;417(6891):876-80
references: 12050675
references: EMBO J. 2009 Sep 2;28(17):2503-10
references: 19629047
references: BMC Mol Biol. 2012 Jul 02;13:23
references: 22747774
references: Biochimie. 2011 Aug;93(8):1239-51
references: 21635933
references: Nucleic Acids Res. 2012 Feb;40(4):1485-98
references: 22021381
references: Sci Rep. 2012;2:1016
references: 23264878
references: Genes Dev. 2011 Feb 1;25(3):220-5
references: 21289067
references: Biochemistry. 2011 Jul 26;50(29):6455-61
references: 21671673
references: Hum Mutat. 2012 Aug;33(8):1302-9
references: 22573514
references: Nat Chem Biol. 2012 Feb 05;8(3):301-10
references: 22306580
references: Am J Hum Genet. 2011 Jul 15;89(1):121-30
references: 21683323
references: Cell Mol Life Sci. 2012 Mar;69(5):697-716
references: 21964926
references: J Biol Chem. 2012 Jan 6;287(2):1007-21
references: 22102414
references: Curr Biol. 2008 Jun 24;18(12):900-5
references: 18538569
references: Biochemistry. 2008 Feb 19;47(7):1896-909
references: 18205402
references: Mol Carcinog. 2009 Apr;48(4):319-25
references: 19306310
references: Cell. 2010 Mar 5;140(5):678-91
references: 20211137
references: Nucleic Acids Res. 2007;35(22):7429-55
references: 17913750
references: Proc Natl Acad Sci U S A. 1962 Dec 15;48:2013-8
references: 13947099
references: Biochem J. 2010 Aug 15;430(1):119-28
references: 20524933
references: Nucleic Acids Res. 2008 Mar;36(4):1321-33
references: 18187510
references: Mol Biosyst. 2009 Dec;5(12):1713-9
references: 19585004
references: J Biol Chem. 1999 Apr 30;274(18):12797-802
references: 10212265
references: Structure. 2012 Dec 5;20(12):2090-102
references: 23085077
references: Mol Biosyst. 2009 Dec;5(12):1703-12
references: 19587895
references: Nucleic Acids Res. 2007;35(2):406-13
references: 17169996