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PMID: 20811343 Published · ppublish English Evaluation Study Journal Article Review

Evaluating genome-scale approaches to eukaryotic DNA replication.

Nature reviews. Genetics ·Vol. 11 ·No. 10 ·2010-10-00 ·Pages 673-84

Gilbert DM

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.

MeSH Terms
Animals DNA Replication/genetics Eukaryotic Cells/metabolism Genome/genetics Genomics/methods Humans Models, Genetic Replication Origin/genetics Reproducibility of Results
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Gilbert David M
Department of Biological Science, Florida State University, Tallahassee, 32306, USA. gilbert@bio.fsu.edu
References (120)
120 references, click to expand
  1. The temporal program of chromosome replication: genomewide replication in clb5{Delta} Saccharomyces cerevisiae.
    Genetics. 2008 Dec;180(4):1833-47 PMID: 18832352
  2. The fission yeast homologue of Orc4p binds to replication origin DNA via multiple AT-hooks.
    Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2656-61 PMID: 10077566
  3. Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication.
    Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):8956-61 PMID: 18579778
  4. Genome-wide characterization of fission yeast DNA replication origins.
    EMBO J. 2006 Nov 1;25(21):5171-9 PMID: 17053780
  5. Genome-wide localization of pre-RC sites and identification of replication origins in fission yeast.
    EMBO J. 2007 Mar 7;26(5):1327-39 PMID: 17304213
  6. Bovine papilloma virus plasmids replicate randomly in mouse fibroblasts throughout S phase of the cell cycle.
    Cell. 1987 Jul 3;50(1):59-68 PMID: 3036365
  7. Checkpoint independence of most DNA replication origins in fission yeast.
    BMC Mol Biol. 2007 Dec 19;8:112 PMID: 18093330
  8. Predictable dynamic program of timing of DNA replication in human cells.
    Genome Res. 2009 Dec;19(12):2288-99 PMID: 19767418
  9. Increased rate of human mutations where DNA and RNA polymerases collide.
    Trends Genet. 2009 Dec;25(12):523-7 PMID: 19853958
  10. Why are we where we are? Understanding replication origins and initiation sites in eukaryotes using ChIP-approaches.
    Chromosome Res. 2010 Jan;18(1):63-77 PMID: 19904620
  11. Replication timing of human chromosome 6.
    Cell Cycle. 2005 Jan;4(1):172-6 PMID: 15611667
  12. Defining replication origin efficiency using DNA fiber assays.
    Chromosome Res. 2010 Jan;18(1):91-102 PMID: 20039120
  13. Excess Mcm2-7 license dormant origins of replication that can be used under conditions of replicative stress.
    J Cell Biol. 2006 Jun 5;173(5):673-83 PMID: 16754955
  14. Genome-organizing factors Top2 and Hmo1 prevent chromosome fragility at sites of S phase transcription.
    Cell. 2009 Sep 4;138(5):870-84 PMID: 19737516
  15. Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae.
    Nat Struct Mol Biol. 2010 Feb;17(2):251-7 PMID: 20118936
  16. DNA topology, not DNA sequence, is a critical determinant for Drosophila ORC-DNA binding.
    EMBO J. 2004 Feb 25;23(4):897-907 PMID: 14765124
  17. Mapping sites where replication initiates in mammalian cells using DNA fibers.
    Exp Cell Res. 2001 Dec 10;271(2):263-8 PMID: 11716538
  18. Replication timing and transcriptional control: beyond cause and effect--part II.
    Curr Opin Genet Dev. 2009 Apr;19(2):142-9 PMID: 19345088
  19. MRC1-dependent scaling of the budding yeast DNA replication timing program.
    Genome Res. 2010 Jun;20(6):781-90 PMID: 20219942
  20. Microarray analysis of DNA replication timing.
    Methods Mol Biol. 2009;556:191-203 PMID: 19488880
  21. Arabidopsis thaliana chromosome 4 replicates in two phases that correlate with chromatin state.
    PLoS Genet. 2010 Jun 10;6(6):e1000982 PMID: 20548960
  22. Genome-wide analysis of DNA synthesis by BrdU immunoprecipitation on tiling microarrays (BrdU-IP-chip) in Saccharomyces cerevisiae.
    Cold Spring Harb Protoc. 2010 Feb;2010(2):pdb.prot5385 PMID: 20150148
  23. Coordination of replication and transcription along a Drosophila chromosome.
    Genes Dev. 2004 Dec 15;18(24):3094-105 PMID: 15601823
  24. A revisionist replicon model for higher eukaryotic genomes.
    J Cell Biochem. 2008 Oct 1;105(2):321-9 PMID: 18680119
  25. The heterochromatin protein Swi6/HP1 activates replication origins at the pericentromeric region and silent mating-type locus.
    Nat Cell Biol. 2009 Mar;11(3):357-62 PMID: 19182789
  26. Genome-wide distribution of ORC and MCM proteins in S. cerevisiae: high-resolution mapping of replication origins.
    Science. 2001 Dec 14;294(5550):2357-60 PMID: 11743203
  27. S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex.
    Nature. 2003 Aug 28;424(6952):1078-83 PMID: 12944972
  28. Uncoupling global and fine-tuning replication timing determinants for mouse pericentric heterochromatin.
    J Cell Biol. 2006 Jul 17;174(2):185-94 PMID: 16831888
  29. Shifts in replication timing actively affect histone acetylation during nucleosome reassembly.
    Mol Cell. 2009 Jun 26;34(6):767-74 PMID: 19560427
  30. Multiplexed lipid dip-pen nanolithography on subcellular scales for the templating of functional proteins and cell culture.
    Small. 2008 Oct;4(10):1785-93 PMID: 18814174
  31. Asymmetric bidirectional replication at the human DBF4 origin.
    Nat Struct Mol Biol. 2008 Jul;15(7):722-9 PMID: 18536724
  32. Timing of replication is a determinant of neutral substitution rates but does not explain slow Y chromosome evolution in rodents.
    Mol Biol Evol. 2010 May;27(5):1077-86 PMID: 20026481
  33. In search of the holy replicator.
    Nat Rev Mol Cell Biol. 2004 Oct;5(10):848-55 PMID: 15459665
  34. Replication in context: dynamic regulation of DNA replication patterns in metazoans.
    Nat Rev Genet. 2007 Aug;8(8):588-600 PMID: 17621316
  35. Replication in hydroxyurea: it's a matter of time.
    Mol Cell Biol. 2007 Sep;27(18):6396-406 PMID: 17636020
  36. A genomic view of eukaryotic DNA replication.
    Chromosome Res. 2005;13(3):309-26 PMID: 15868424
  37. Global reorganization of replication domains during embryonic stem cell differentiation.
    PLoS Biol. 2008 Oct 7;6(10):e245 PMID: 18842067
  38. Promiscuous initiation on mammalian chromosomal DNA templates and its possible suppression by transcription.
    Exp Cell Res. 2005 Aug 1;308(1):53-64 PMID: 15904920
  39. Genome-wide studies highlight indirect links between human replication origins and gene regulation.
    Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15837-42 PMID: 18838675
  40. Genome-wide DNA replication profile for Drosophila melanogaster: a link between transcription and replication timing.
    Nat Genet. 2002 Nov;32(3):438-42 PMID: 12355067
  41. Replication initiation point mapping.
    Methods. 1997 Nov;13(3):271-80 PMID: 9441853
  42. A three-dimensional model of the yeast genome.
    Nature. 2010 May 20;465(7296):363-7 PMID: 20436457
  43. Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome.
    Genes Dev. 2009 Mar 1;23(5):589-601 PMID: 19270159
  44. G2 phase chromatin lacks determinants of replication timing.
    J Cell Biol. 2010 Jun 14;189(6):967-80 PMID: 20530209
  45. G9a selectively represses a class of late-replicating genes at the nuclear periphery.
    Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19363-8 PMID: 19889976
  46. A comprehensive genome-wide map of autonomously replicating sequences in a naive genome.
    PLoS Genet. 2010 May 13;6(5):e1000946 PMID: 20485513
  47. Incorporation into the prereplicative complex activates the Mcm2-7 helicase for Cdc7-Dbf4 phosphorylation.
    Genes Dev. 2009 Mar 1;23(5):643-54 PMID: 19270162
  48. Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes.
    Genome Res. 2010 Apr;20(4):447-57 PMID: 20103589
  49. Replicon dynamics, dormant origin firing, and terminal fork integrity after double-strand break formation.
    Cell. 2009 Apr 17;137(2):247-58 PMID: 19361851
  50. Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication.
    Nat Cell Biol. 2006 Feb;8(2):148-55 PMID: 16429127
  51. Replication origin plasticity, Taylor-made: inhibition vs recruitment of origins under conditions of replication stress.
    Chromosoma. 2007 Aug;116(4):341-7 PMID: 17404750
  52. Isolating apparently pure libraries of replication origins from complex genomes.
    Mol Cell. 2006 Mar 3;21(5):719-26 PMID: 16507369
  53. The relationship between DNA replication and human genome organization.
    Mol Biol Evol. 2009 Apr;26(4):729-41 PMID: 19126867
  54. Global organization of replication time zones of the mouse genome.
    Genome Res. 2008 Oct;18(10):1562-70 PMID: 18669478
  55. Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription.
    Nat Cell Biol. 2009 Nov;11(11):1315-24 PMID: 19838172
  56. Sequence-independent DNA binding and replication initiation by the human origin recognition complex.
    Genes Dev. 2003 Aug 1;17(15):1894-908 PMID: 12897055
  57. Replication initiation patterns in the beta-globin loci of totipotent and differentiated murine cells: evidence for multiple initiation regions.
    Mol Cell Biol. 2002 Jan;22(2):442-52 PMID: 11756541
  58. Human gene organization driven by the coordination of replication and transcription.
    Genome Res. 2007 Sep;17(9):1278-85 PMID: 17675363
  59. Replication fork movement sets chromatin loop size and origin choice in mammalian cells.
    Nature. 2008 Sep 25;455(7212):557-60 PMID: 18716622
  60. DNA replication origins in the Schizosaccharomyces pombe genome.
    Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):337-42 PMID: 15623550
  61. To promote and protect: coordinating DNA replication and transcription for genome stability.
    Epigenetics. 2009 Aug 16;4(6):362-5 PMID: 19736523
  62. Genome-wide analysis of the replication program in mammals.
    Chromosome Res. 2010 Jan;18(1):115-25 PMID: 20205353
  63. Genome-wide kinetics of nucleosome turnover determined by metabolic labeling of histones.
    Science. 2010 May 28;328(5982):1161-4 PMID: 20508129
  64. Genomic study of replication initiation in human chromosomes reveals the influence of transcription regulation and chromatin structure on origin selection.
    Mol Biol Cell. 2010 Feb 1;21(3):393-404 PMID: 19955211
  65. Highly transcribed RNA polymerase II genes are impediments to replication fork progression in Saccharomyces cerevisiae.
    Mol Cell. 2009 Jun 26;34(6):722-34 PMID: 19560424
  66. Genome-wide identification of Isw2 chromatin-remodeling targets by localization of a catalytically inactive mutant.
    Genes Dev. 2005 Apr 15;19(8):942-54 PMID: 15833917
  67. Transcription initiation activity sets replication origin efficiency in mammalian cells.
    PLoS Genet. 2009 Apr;5(4):e1000446 PMID: 19360092
  68. Evolutionarily conserved replication timing profiles predict long-range chromatin interactions and distinguish closely related cell types.
    Genome Res. 2010 Jun;20(6):761-70 PMID: 20430782
  69. Prediction of Saccharomyces cerevisiae replication origins.
    Genome Biol. 2004;5(4):R22 PMID: 15059255
  70. Conserved nucleosome positioning defines replication origins.
    Genes Dev. 2010 Apr 15;24(8):748-53 PMID: 20351051
  71. Sequencing newly replicated DNA reveals widespread plasticity in human replication timing.
    Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):139-44 PMID: 19966280
  72. Structural diversity and dynamics of genomic replication origins in Schizosaccharomyces pombe.
    EMBO J. 2010 Mar 3;29(5):934-42 PMID: 20094030
  73. Genome-wide dynamics of replication timing revealed by in vitro models of mouse embryogenesis.
    Genome Res. 2010 Feb;20(2):155-69 PMID: 19952138
  74. Completion of replication map of Saccharomyces cerevisiae chromosome III.
    Mol Biol Cell. 2001 Nov;12(11):3317-27 PMID: 11694569
  75. Replication profile of Saccharomyces cerevisiae chromosome VI.
    Genes Cells. 1997 Nov;2(11):667-78 PMID: 9491801
  76. The impact of chromatin modifiers on the timing of locus replication in mouse embryonic stem cells.
    Genome Biol. 2007;8(8):R169 PMID: 17705870
  77. Position effects on the timing of replication of chromosomally integrated simian virus 40 molecules in Chinese hamster cells.
    Mol Cell Biol. 1990 Aug;10(8):4345-55 PMID: 2164638
  78. Autoradiography of chromosomal DNA fibers from Chinese hamster cells.
    Proc Natl Acad Sci U S A. 1966 Mar;55(3):599-606 PMID: 5221245
  79. Establishing the program of origin firing during S phase in fission Yeast.
    Cell. 2009 Mar 6;136(5):852-64 PMID: 19269364
  80. Mathematical modelling of eukaryotic DNA replication.
    Chromosome Res. 2010 Jan;18(1):147-61 PMID: 20205354
  81. Dynamics of DNA replication in mammalian somatic cells: nucleotide pool modulates origin choice and interorigin spacing.
    Cell. 2003 Aug 8;114(3):385-94 PMID: 12914702
  82. Multiple functional elements comprise a Mammalian chromosomal replicator.
    Mol Cell Biol. 2003 Mar;23(5):1832-42 PMID: 12589000
  83. Domain-wide regulation of DNA replication timing during mammalian development.
    Chromosome Res. 2010 Jan;18(1):127-36 PMID: 20013151
  84. Heterochromatin protein 1 (HP1) modulates replication timing of the Drosophila genome.
    Genome Res. 2010 Jun;20(6):771-80 PMID: 20435908
  85. DNA replication origins fire stochastically in fission yeast.
    Mol Biol Cell. 2006 Jan;17(1):308-16 PMID: 16251353
  86. Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin.
    Nat Struct Mol Biol. 2004 Nov;11(11):1076-83 PMID: 15475964
  87. Progressive activation of DNA replication initiation in large domains of the immunoglobulin heavy chain locus during B cell development.
    Mol Cell. 2005 Nov 23;20(4):575-87 PMID: 16307921
  88. Temporal regulation of DNA replication in mammalian cells.
    Crit Rev Biochem Mol Biol. 2009 Sep-Oct;44(5):343-51 PMID: 19780641
  89. Interplay between DNA replication and gene expression: a harmonious coexistence.
    Curr Opin Cell Biol. 2010 Jun;22(3):277-83 PMID: 20363609
  90. Genome-wide identification of replication origins in yeast by comparative genomics.
    Genes Dev. 2006 Jul 15;20(14):1874-9 PMID: 16847347
  91. Mapping of early firing origins on a replication profile of budding yeast.
    Genes Cells. 2002 Aug;7(8):781-9 PMID: 12167157
  92. Heritable gene silencing in lymphocytes delays chromatid resolution without affecting the timing of DNA replication.
    Nat Cell Biol. 2003 Jul;5(7):668-74 PMID: 12833066
  93. Replication initiation point mapping: approach and implications.
    Methods Mol Biol. 2009;521:105-20 PMID: 19563103
  94. Defined sequence modules and an architectural element cooperate to promote initiation at an ectopic mammalian chromosomal replication origin.
    Mol Cell Biol. 2004 May;24(10):4138-50 PMID: 15121836
  95. Isolation of restriction fragments containing origins of replication from complex genomes.
    Methods Mol Biol. 2009;521:315-28 PMID: 19563114
  96. DNA replication origin interference increases the spacing between initiation events in human cells.
    Mol Biol Cell. 2006 Dec;17(12):5337-45 PMID: 17005913
  97. BRG1 co-localizes with DNA replication factors and is required for efficient replication fork progression.
    Nucleic Acids Res. 2010 Nov;38(20):6906-19 PMID: 20571081
  98. Autonomous replication in human cells of multimers of specific human and bacterial DNA sequences.
    Mol Cell Biol. 1993 May;13(5):2688-96 PMID: 8386315
  99. Decreased replication origin activity in temporal transition regions.
    J Cell Biol. 2009 Nov 30;187(5):623-35 PMID: 19951913
  100. High-throughput mapping of origins of replication in human cells.
    EMBO Rep. 2007 Aug;8(8):770-7 PMID: 17668008
  101. Predicting human nucleosome occupancy from primary sequence.
    PLoS Comput Biol. 2008 Aug 22;4(8):e1000134 PMID: 18725940
  102. Single molecule epigenetic analysis in a nanofluidic channel.
    Anal Chem. 2010 Mar 15;82(6):2480-7 PMID: 20184350
  103. Modular structure of the human lamin B2 replicator.
    Mol Cell Biol. 2004 Apr;24(7):2958-67 PMID: 15024083
  104. Replication timing of the human genome.
    Hum Mol Genet. 2004 Jan 15;13(2):191-202 PMID: 14645202
  105. Temporal order of replication of Xenopus laevis 5S ribosomal RNA genes in somatic cells.
    Proc Natl Acad Sci U S A. 1986 May;83(9):2924-8 PMID: 3458252
  106. Genome-wide replication profiles indicate an expansive role for Rpd3L in regulating replication initiation timing or efficiency, and reveal genomic loci of Rpd3 function in Saccharomyces cerevisiae.
    Genes Dev. 2009 May 1;23(9):1077-90 PMID: 19417103
  107. Genome-wide approaches to determining origin distribution.
    Chromosome Res. 2010 Jan;18(1):79-89 PMID: 19921448
  108. Association of fragile X syndrome with delayed replication of the FMR1 gene.
    Cell. 1993 Jul 2;73(7):1403-9 PMID: 8324827
  109. Making sense of eukaryotic DNA replication origins.
    Science. 2001 Oct 5;294(5540):96-100 PMID: 11588251
  110. Replication timing as an epigenetic mark.
    Epigenetics. 2009 Feb 16;4(2):93-7 PMID: 19242104
  111. Pan-S replication patterns and chromosomal domains defined by genome-tiling arrays of ENCODE genomic areas.
    Genome Res. 2007 Jun;17(6):865-76 PMID: 17568004
  112. Genome-wide mapping of ORC and Mcm2p binding sites on tiling arrays and identification of essential ARS consensus sequences in S. cerevisiae.
    BMC Genomics. 2006 Oct 26;7:276 PMID: 17067396
  113. Molecular analysis of the replication program in unicellular model organisms.
    Chromosome Res. 2010 Jan;18(1):19-34 PMID: 20012185
  114. Eukaryotic chromosome DNA replication: where, when, and how?
    Annu Rev Biochem. 2010;79:89-130 PMID: 20373915
  115. The chromatin remodeling complex NoRC controls replication timing of rRNA genes.
    EMBO J. 2005 Jan 12;24(1):120-7 PMID: 15577942
  116. Comparative analysis of DNA replication timing reveals conserved large-scale chromosomal architecture.
    PLoS Genet. 2010 Jul 01;6(7):e1001011 PMID: 20617169
  117. Generating highly ordered DNA nanostrand arrays.
    Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18321-5 PMID: 16352724
  118. Drosophila ORC localizes to open chromatin and marks sites of cohesin complex loading.
    Genome Res. 2010 Feb;20(2):201-11 PMID: 19996087
  119. Plasticity of DNA replication initiation in Epstein-Barr virus episomes.
    PLoS Biol. 2004 Jun;2(6):e152 PMID: 15208711
  120. The Chinese hamster dihydrofolate reductase replication origin decision point follows activation of transcription and suppresses initiation of replication within transcription units.
    Mol Cell Biol. 2006 Feb;26(3):1051-62 PMID: 16428457
Article Info
Journal
Nature reviews. Genetics
Abbr.
Nat Rev Genet
ISSN
1471-0064
DOI
10.1038/nrg2830
Email
gilbert@bio.fsu.edu
Published
2010-10-00
Epub
2010-00-01
Pages
673-84
Language
English
Region
England
NLM ID
100962779
PMCID
PMC2962615
Subset
IM
Grants
NIGMS NIH HHS · P01 GM085354 · United States
NIGMS NIH HHS · P01 GM085354-020002 · United States
NIGMS NIH HHS · R01 GM083337 · United States
NIGMS NIH HHS · R01 GM083337-03 · United States
External Links
PubMed source DOI: 10.1038/nrg2830 PMC Full Text View journal details
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