title: Evaluating genome-scale approaches to eukaryotic DNA replication.
abstract: Mechanisms regulating where and when eukaryotic DNA replication initiates remain a mystery. Recently, genome-scale methods have been brought to bear on this problem. The identification of replication origins and their associated proteins in yeasts is a well-integrated investigative tool, but corresponding data sets from multicellular organisms are scarce. By contrast, standardized protocols for evaluating replication timing have generated informative data sets for most eukaryotic systems. Here, I summarize the genome-scale methods that are most frequently used to analyse replication in eukaryotes, the kinds of questions each method can address and the technical hurdles that must be overcome to gain a complete understanding of the nature of eukaryotic replication origins.
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, 32306, USA. gilbert@bio.fsu.edu
authors.forename: David M
authors.initials: DM
authors.lastname: Gilbert
mesh_terms: D000818:Animals; D004261:DNA Replication / Q000235:genetics*; D005057:Eukaryotic Cells / Q000378:metabolism*; D016678:Genome / Q000235:genetics; D023281:Genomics / Q000379:methods*; D006801:Humans; D008957:Models, Genetic; D018741:Replication Origin / Q000235:genetics*; D015203:Reproducibility of Results
references.citation: Genetics. 2008 Dec;180(4):1833-47
references.pmid: 18832352
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2656-61
references.pmid: 10077566
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):8956-61
references.pmid: 18579778
references.citation: EMBO J. 2006 Nov 1;25(21):5171-9
references.pmid: 17053780
references.citation: EMBO J. 2007 Mar 7;26(5):1327-39
references.pmid: 17304213
references.citation: Cell. 1987 Jul 3;50(1):59-68
references.pmid: 3036365
references.citation: BMC Mol Biol. 2007 Dec 19;8:112
references.pmid: 18093330
references.citation: Genome Res. 2009 Dec;19(12):2288-99
references.pmid: 19767418
references.citation: Trends Genet. 2009 Dec;25(12):523-7
references.pmid: 19853958
references.citation: Chromosome Res. 2010 Jan;18(1):63-77
references.pmid: 19904620
references.citation: Cell Cycle. 2005 Jan;4(1):172-6
references.pmid: 15611667
references.citation: Chromosome Res. 2010 Jan;18(1):91-102
references.pmid: 20039120
references.citation: J Cell Biol. 2006 Jun 5;173(5):673-83
references.pmid: 16754955
references.citation: Cell. 2009 Sep 4;138(5):870-84
references.pmid: 19737516
references.citation: Nat Struct Mol Biol. 2010 Feb;17(2):251-7
references.pmid: 20118936
references.citation: EMBO J. 2004 Feb 25;23(4):897-907
references.pmid: 14765124
references.citation: Exp Cell Res. 2001 Dec 10;271(2):263-8
references.pmid: 11716538
references.citation: Curr Opin Genet Dev. 2009 Apr;19(2):142-9
references.pmid: 19345088
references.citation: Genome Res. 2010 Jun;20(6):781-90
references.pmid: 20219942
references.citation: Methods Mol Biol. 2009;556:191-203
references.pmid: 19488880
references.citation: PLoS Genet. 2010 Jun 10;6(6):e1000982
references.pmid: 20548960
references.citation: Cold Spring Harb Protoc. 2010 Feb;2010(2):pdb.prot5385
references.pmid: 20150148
references.citation: Genes Dev. 2004 Dec 15;18(24):3094-105
references.pmid: 15601823
references.citation: J Cell Biochem. 2008 Oct 1;105(2):321-9
references.pmid: 18680119
references.citation: Nat Cell Biol. 2009 Mar;11(3):357-62
references.pmid: 19182789
references.citation: Science. 2001 Dec 14;294(5550):2357-60
references.pmid: 11743203
references.citation: Nature. 2003 Aug 28;424(6952):1078-83
references.pmid: 12944972
references.citation: J Cell Biol. 2006 Jul 17;174(2):185-94
references.pmid: 16831888
references.citation: Mol Cell. 2009 Jun 26;34(6):767-74
references.pmid: 19560427
references.citation: Small. 2008 Oct;4(10):1785-93
references.pmid: 18814174
references.citation: Nat Struct Mol Biol. 2008 Jul;15(7):722-9
references.pmid: 18536724
references.citation: Mol Biol Evol. 2010 May;27(5):1077-86
references.pmid: 20026481
references.citation: Nat Rev Mol Cell Biol. 2004 Oct;5(10):848-55
references.pmid: 15459665
references.citation: Nat Rev Genet. 2007 Aug;8(8):588-600
references.pmid: 17621316
references.citation: Mol Cell Biol. 2007 Sep;27(18):6396-406
references.pmid: 17636020
references.citation: Chromosome Res. 2005;13(3):309-26
references.pmid: 15868424
references.citation: PLoS Biol. 2008 Oct 7;6(10):e245
references.pmid: 18842067
references.citation: Exp Cell Res. 2005 Aug 1;308(1):53-64
references.pmid: 15904920
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15837-42
references.pmid: 18838675
references.citation: Nat Genet. 2002 Nov;32(3):438-42
references.pmid: 12355067
references.citation: Methods. 1997 Nov;13(3):271-80
references.pmid: 9441853
references.citation: Nature. 2010 May 20;465(7296):363-7
references.pmid: 20436457
references.citation: Genes Dev. 2009 Mar 1;23(5):589-601
references.pmid: 19270159
references.citation: J Cell Biol. 2010 Jun 14;189(6):967-80
references.pmid: 20530209
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19363-8
references.pmid: 19889976
references.citation: PLoS Genet. 2010 May 13;6(5):e1000946
references.pmid: 20485513
references.citation: Genes Dev. 2009 Mar 1;23(5):643-54
references.pmid: 19270162
references.citation: Genome Res. 2010 Apr;20(4):447-57
references.pmid: 20103589
references.citation: Cell. 2009 Apr 17;137(2):247-58
references.pmid: 19361851
references.citation: Nat Cell Biol. 2006 Feb;8(2):148-55
references.pmid: 16429127
references.citation: Chromosoma. 2007 Aug;116(4):341-7
references.pmid: 17404750
references.citation: Mol Cell. 2006 Mar 3;21(5):719-26
references.pmid: 16507369
references.citation: Mol Biol Evol. 2009 Apr;26(4):729-41
references.pmid: 19126867
references.citation: Genome Res. 2008 Oct;18(10):1562-70
references.pmid: 18669478
references.citation: Nat Cell Biol. 2009 Nov;11(11):1315-24
references.pmid: 19838172
references.citation: Genes Dev. 2003 Aug 1;17(15):1894-908
references.pmid: 12897055
references.citation: Mol Cell Biol. 2002 Jan;22(2):442-52
references.pmid: 11756541
references.citation: Genome Res. 2007 Sep;17(9):1278-85
references.pmid: 17675363
references.citation: Nature. 2008 Sep 25;455(7212):557-60
references.pmid: 18716622
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):337-42
references.pmid: 15623550
references.citation: Epigenetics. 2009 Aug 16;4(6):362-5
references.pmid: 19736523
references.citation: Chromosome Res. 2010 Jan;18(1):115-25
references.pmid: 20205353
references.citation: Science. 2010 May 28;328(5982):1161-4
references.pmid: 20508129
references.citation: Mol Biol Cell. 2010 Feb 1;21(3):393-404
references.pmid: 19955211
references.citation: Mol Cell. 2009 Jun 26;34(6):722-34
references.pmid: 19560424
references.citation: Genes Dev. 2005 Apr 15;19(8):942-54
references.pmid: 15833917
references.citation: PLoS Genet. 2009 Apr;5(4):e1000446
references.pmid: 19360092
references.citation: Genome Res. 2010 Jun;20(6):761-70
references.pmid: 20430782
references.citation: Genome Biol. 2004;5(4):R22
references.pmid: 15059255
references.citation: Genes Dev. 2010 Apr 15;24(8):748-53
references.pmid: 20351051
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):139-44
references.pmid: 19966280
references.citation: EMBO J. 2010 Mar 3;29(5):934-42
references.pmid: 20094030
references.citation: Genome Res. 2010 Feb;20(2):155-69
references.pmid: 19952138
references.citation: Mol Biol Cell. 2001 Nov;12(11):3317-27
references.pmid: 11694569
references.citation: Genes Cells. 1997 Nov;2(11):667-78
references.pmid: 9491801
references.citation: Genome Biol. 2007;8(8):R169
references.pmid: 17705870
references.citation: Mol Cell Biol. 1990 Aug;10(8):4345-55
references.pmid: 2164638
references.citation: Proc Natl Acad Sci U S A. 1966 Mar;55(3):599-606
references.pmid: 5221245
references.citation: Cell. 2009 Mar 6;136(5):852-64
references.pmid: 19269364
references.citation: Chromosome Res. 2010 Jan;18(1):147-61
references.pmid: 20205354
references.citation: Cell. 2003 Aug 8;114(3):385-94
references.pmid: 12914702
references.citation: Mol Cell Biol. 2003 Mar;23(5):1832-42
references.pmid: 12589000
references.citation: Chromosome Res. 2010 Jan;18(1):127-36
references.pmid: 20013151
references.citation: Genome Res. 2010 Jun;20(6):771-80
references.pmid: 20435908
references.citation: Mol Biol Cell. 2006 Jan;17(1):308-16
references.pmid: 16251353
references.citation: Nat Struct Mol Biol. 2004 Nov;11(11):1076-83
references.pmid: 15475964
references.citation: Mol Cell. 2005 Nov 23;20(4):575-87
references.pmid: 16307921
references.citation: Crit Rev Biochem Mol Biol. 2009 Sep-Oct;44(5):343-51
references.pmid: 19780641
references.citation: Curr Opin Cell Biol. 2010 Jun;22(3):277-83
references.pmid: 20363609
references.citation: Genes Dev. 2006 Jul 15;20(14):1874-9
references.pmid: 16847347
references.citation: Genes Cells. 2002 Aug;7(8):781-9
references.pmid: 12167157
references.citation: Nat Cell Biol. 2003 Jul;5(7):668-74
references.pmid: 12833066
references.citation: Methods Mol Biol. 2009;521:105-20
references.pmid: 19563103
references.citation: Mol Cell Biol. 2004 May;24(10):4138-50
references.pmid: 15121836
references.citation: Methods Mol Biol. 2009;521:315-28
references.pmid: 19563114
references.citation: Mol Biol Cell. 2006 Dec;17(12):5337-45
references.pmid: 17005913
references.citation: Nucleic Acids Res. 2010 Nov;38(20):6906-19
references.pmid: 20571081
references.citation: Mol Cell Biol. 1993 May;13(5):2688-96
references.pmid: 8386315
references.citation: J Cell Biol. 2009 Nov 30;187(5):623-35
references.pmid: 19951913
references.citation: EMBO Rep. 2007 Aug;8(8):770-7
references.pmid: 17668008
references.citation: PLoS Comput Biol. 2008 Aug 22;4(8):e1000134
references.pmid: 18725940
references.citation: Anal Chem. 2010 Mar 15;82(6):2480-7
references.pmid: 20184350
references.citation: Mol Cell Biol. 2004 Apr;24(7):2958-67
references.pmid: 15024083
references.citation: Hum Mol Genet. 2004 Jan 15;13(2):191-202
references.pmid: 14645202
references.citation: Proc Natl Acad Sci U S A. 1986 May;83(9):2924-8
references.pmid: 3458252
references.citation: Genes Dev. 2009 May 1;23(9):1077-90
references.pmid: 19417103
references.citation: Chromosome Res. 2010 Jan;18(1):79-89
references.pmid: 19921448
references.citation: Cell. 1993 Jul 2;73(7):1403-9
references.pmid: 8324827
references.citation: Science. 2001 Oct 5;294(5540):96-100
references.pmid: 11588251
references.citation: Epigenetics. 2009 Feb 16;4(2):93-7
references.pmid: 19242104
references.citation: Genome Res. 2007 Jun;17(6):865-76
references.pmid: 17568004
references.citation: BMC Genomics. 2006 Oct 26;7:276
references.pmid: 17067396
references.citation: Chromosome Res. 2010 Jan;18(1):19-34
references.pmid: 20012185
references.citation: Annu Rev Biochem. 2010;79:89-130
references.pmid: 20373915
references.citation: EMBO J. 2005 Jan 12;24(1):120-7
references.pmid: 15577942
references.citation: PLoS Genet. 2010 Jul 01;6(7):e1001011
references.pmid: 20617169
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18321-5
references.pmid: 16352724
references.citation: Genome Res. 2010 Feb;20(2):201-11
references.pmid: 19996087
references.citation: PLoS Biol. 2004 Jun;2(6):e152
references.pmid: 15208711
references.citation: Mol Cell Biol. 2006 Feb;26(3):1051-62
references.pmid: 16428457