3D Replicon Distributions Arise from Stochastic Initiation and Domino-like DNA Replication Progression

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Apr 8

PMID 27052359

Citations 36

Authors

D Lob

N Lengert

V O Chagin

M Reinhart

C S Casas-Delucchi

M C Cardoso

B Drossel

Affiliations

Soon will be listed here.

Abstract

DNA replication dynamics in cells from higher eukaryotes follows very complex but highly efficient mechanisms. However, the principles behind initiation of potential replication origins and emergence of typical patterns of nuclear replication sites remain unclear. Here, we propose a comprehensive model of DNA replication in human cells that is based on stochastic, proximity-induced replication initiation. Critical model features are: spontaneous stochastic firing of individual origins in euchromatin and facultative heterochromatin, inhibition of firing at distances below the size of chromatin loops and a domino-like effect by which replication forks induce firing of nearby origins. The model reproduces the empirical temporal and chromatin-related properties of DNA replication in human cells. We advance the one-dimensional DNA replication model to a spatial model by taking into account chromatin folding in the nucleus, and we are able to reproduce the spatial and temporal characteristics of the replication foci distribution throughout S-phase.

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References

Guilbaud G, Rappailles A, Baker A, Chen C, Arneodo A, Goldar A . Evidence for sequential and increasing activation of replication origins along replication timing gradients in the human genome. PLoS Comput Biol. 2012; 7(12):e1002322. PMC: 3248390. DOI: 10.1371/journal.pcbi.1002322. View

J Blow J, Gillespie P, Francis D, Jackson D . Replication origins in Xenopus egg extract Are 5-15 kilobases apart and are activated in clusters that fire at different times. J Cell Biol. 2001; 152(1):15-25. PMC: 2193667. DOI: 10.1083/jcb.152.1.15. View

Pope B, Ryba T, Dileep V, Yue F, Wu W, Denas O . Topologically associating domains are stable units of replication-timing regulation. Nature. 2014; 515(7527):402-5. PMC: 4251741. DOI: 10.1038/nature13986. View

Duan Z, Blau C . The genome in space and time: does form always follow function? How does the spatial and temporal organization of a eukaryotic genome reflect and influence its functions?. Bioessays. 2012; 34(9):800-10. PMC: 3638008. DOI: 10.1002/bies.201200034. View

Dewar J, Walter J . Chromosome biology: conflict management for replication and transcription. Curr Biol. 2013; 23(5):R200-2. DOI: 10.1016/j.cub.2013.01.054. View

Casas-Delucchi C, Brero A, Rahn H, Solovei I, Wutz A, Cremer T . Histone acetylation controls the inactive X chromosome replication dynamics. Nat Commun. 2011; 2:222. PMC: 3072080. DOI: 10.1038/ncomms1218. View

Sporbert A, Gahl A, Ankerhold R, Leonhardt H, Cardoso M . DNA polymerase clamp shows little turnover at established replication sites but sequential de novo assembly at adjacent origin clusters. Mol Cell. 2002; 10(6):1355-65. DOI: 10.1016/s1097-2765(02)00729-3. View

Paulson J, Laemmli U . The structure of histone-depleted metaphase chromosomes. Cell. 1977; 12(3):817-28. DOI: 10.1016/0092-8674(77)90280-x. View

Earnshaw W, Laemmli U . Architecture of metaphase chromosomes and chromosome scaffolds. J Cell Biol. 1983; 96(1):84-93. PMC: 2112267. DOI: 10.1083/jcb.96.1.84. View

10.

DePamphilis M . Replication origins in metazoan chromosomes: fact or fiction?. Bioessays. 1999; 21(1):5-16. DOI: 10.1002/(SICI)1521-1878(199901)21:1<5::AID-BIES2>3.0.CO;2-6. View

11.

Spiesser T, Klipp E, Barberis M . A model for the spatiotemporal organization of DNA replication in Saccharomyces cerevisiae. Mol Genet Genomics. 2009; 282(1):25-35. PMC: 2695552. DOI: 10.1007/s00438-009-0443-9. View

12.

Bickmore W, Carothers A . Factors affecting the timing and imprinting of replication on a mammalian chromosome. J Cell Sci. 1995; 108 ( Pt 8):2801-9. DOI: 10.1242/jcs.108.8.2801. View

13.

Cardoso M, Leonhardt H, Nadal-Ginard B . Reversal of terminal differentiation and control of DNA replication: cyclin A and Cdk2 specifically localize at subnuclear sites of DNA replication. Cell. 1993; 74(6):979-92. DOI: 10.1016/0092-8674(93)90721-2. View

14.

Rego A, Sinclair P, Tao W, Kireev I, Belmont A . The facultative heterochromatin of the inactive X chromosome has a distinctive condensed ultrastructure. J Cell Sci. 2008; 121(Pt 7):1119-27. DOI: 10.1242/jcs.026104. View

15.

Blow J, Dutta A . Preventing re-replication of chromosomal DNA. Nat Rev Mol Cell Biol. 2005; 6(6):476-86. PMC: 2688777. DOI: 10.1038/nrm1663. View

16.

Aladjem M, Fanning E . The replicon revisited: an old model learns new tricks in metazoan chromosomes. EMBO Rep. 2004; 5(7):686-91. PMC: 1299096. DOI: 10.1038/sj.embor.7400185. View

17.

Goldar A, Labit H, Marheineke K, Hyrien O . A dynamic stochastic model for DNA replication initiation in early embryos. PLoS One. 2008; 3(8):e2919. PMC: 2488399. DOI: 10.1371/journal.pone.0002919. View

18.

Takebayashi S, Sugimura K, Saito T, Sato C, Fukushima Y, Taguchi H . Regulation of replication at the R/G chromosomal band boundary and pericentromeric heterochromatin of mammalian cells. Exp Cell Res. 2005; 304(1):162-74. DOI: 10.1016/j.yexcr.2004.10.024. View

19.

Machida Y, Hamlin J, Dutta A . Right place, right time, and only once: replication initiation in metazoans. Cell. 2005; 123(1):13-24. DOI: 10.1016/j.cell.2005.09.019. View

20.

Chagin V, Casas-Delucchi C, Reinhart M, Schermelleh L, Markaki Y, Maiser A . 4D Visualization of replication foci in mammalian cells corresponding to individual replicons. Nat Commun. 2016; 7:11231. PMC: 4829660. DOI: 10.1038/ncomms11231. View