Clusters, Factories and Domains: The Complex Structure of S-phase Comes into Focus

Overview

Journal Cell Cycle

Specialty Cell Biology

Date 2010 Aug 21

PMID 20724827

Citations 28

Authors

Peter J Gillespie

J Julian Blow

Affiliations

Soon will be listed here.

Abstract

During S-phase of the cell cycle, chromosomal DNA is replicated according to a complex replication timing program, with megabase-sized domains replicating at different times. DNA fibre analysis reveals that clusters of adjacent replication origins fire near-synchronously. Analysis of replicating cells by light microscopy shows that DNA synthesis occurs in discrete foci or factories. The relationship between timing domains, origin clusters and replication foci is currently unclear. Recent work, using a hybrid Xenopus/hamster replication system, has shown that when CDK levels are manipulated during S-phase the activation of replication factories can be uncoupled from progression through the replication timing program. Here, we use data from this hybrid system to investigate potential relationships between timing domains, origin clusters and replication foci. We suggest that each timing domain typically comprises several replicon clusters, which are usually processed sequentially by replication factories. We discuss how replication might be regulated at different levels to create this complex organisation and the potential involvement of CDKs in this process.

Citing Articles

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ATXN3 controls DNA replication and transcription by regulating chromatin structure.

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Ctf4 organizes sister replisomes and Pol α into a replication factory.

Yuan Z, Georgescu R, de Luna Almeida Santos R, Zhang D, Bai L, Yao N Elife. 2019; 8.

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References

Lande-Diner L, Zhang J, Cedar H . Shifts in replication timing actively affect histone acetylation during nucleosome reassembly. Mol Cell. 2009; 34(6):767-74. PMC: 2717743. DOI: 10.1016/j.molcel.2009.05.027. View

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

Hiratani I, Ryba T, Itoh M, Yokochi T, Schwaiger M, Chang C . Global reorganization of replication domains during embryonic stem cell differentiation. PLoS Biol. 2008; 6(10):e245. PMC: 2561079. DOI: 10.1371/journal.pbio.0060245. View

Dimitrova D, Gilbert D . Temporally coordinated assembly and disassembly of replication factories in the absence of DNA synthesis. Nat Cell Biol. 2000; 2(10):686-94. PMC: 1255923. DOI: 10.1038/35036309. View

Gilbert D, Miyazawa H, DePamphilis M . Site-specific initiation of DNA replication in Xenopus egg extract requires nuclear structure. Mol Cell Biol. 1995; 15(6):2942-54. PMC: 230525. DOI: 10.1128/MCB.15.6.2942. View

White E, Emanuelsson O, Scalzo D, Royce T, Kosak S, Oakeley E . DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states. Proc Natl Acad Sci U S A. 2004; 101(51):17771-6. PMC: 539744. DOI: 10.1073/pnas.0408170101. View

Erlandsson F, Linnman C, Ekholm S, Bengtsson E, Zetterberg A . A detailed analysis of cyclin A accumulation at the G(1)/S border in normal and transformed cells. Exp Cell Res. 2000; 259(1):86-95. DOI: 10.1006/excr.2000.4889. View

Kitamura E, Blow J, Tanaka T . Live-cell imaging reveals replication of individual replicons in eukaryotic replication factories. Cell. 2006; 125(7):1297-308. PMC: 3019746. DOI: 10.1016/j.cell.2006.04.041. View

Hiratani I, Ryba T, Itoh M, Rathjen J, Kulik M, Papp B . Genome-wide dynamics of replication timing revealed by in vitro models of mouse embryogenesis. Genome Res. 2009; 20(2):155-69. PMC: 2813472. DOI: 10.1101/gr.099796.109. View

10.

Somanathan S, Suchyna T, Siegel A, Berezney R . Targeting of PCNA to sites of DNA replication in the mammalian cell nucleus. J Cell Biochem. 2001; 81(1):56-67. DOI: 10.1002/1097-4644(20010401)81:1<56::aid-jcb1023>3.0.co;2-#. View

11.

Pope B, Hiratani I, Gilbert D . Domain-wide regulation of DNA replication timing during mammalian development. Chromosome Res. 2009; 18(1):127-36. PMC: 2827620. DOI: 10.1007/s10577-009-9100-8. View

12.

Zhang J, Xu F, Hashimshony T, Keshet I, Cedar H . Establishment of transcriptional competence in early and late S phase. Nature. 2002; 420(6912):198-202. DOI: 10.1038/nature01150. View

13.

Karnani N, Taylor C, Malhotra A, Dutta A . Pan-S replication patterns and chromosomal domains defined by genome-tiling arrays of ENCODE genomic areas. Genome Res. 2007; 17(6):865-76. PMC: 1891345. DOI: 10.1101/gr.5427007. View

14.

Ibarra A, Schwob E, Mendez J . Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication. Proc Natl Acad Sci U S A. 2008; 105(26):8956-61. PMC: 2449346. DOI: 10.1073/pnas.0803978105. View

15.

Desprat R, Thierry-Mieg D, Lailler N, Lajugie J, Schildkraut C, Thierry-Mieg J . Predictable dynamic program of timing of DNA replication in human cells. Genome Res. 2009; 19(12):2288-99. PMC: 2792175. DOI: 10.1101/gr.094060.109. View

16.

Strausfeld U, Howell M, Descombes P, Chevalier S, Rempel R, ADAMCZEWSKI J . Both cyclin A and cyclin E have S-phase promoting (SPF) activity in Xenopus egg extracts. J Cell Sci. 1996; 109 ( Pt 6):1555-63. DOI: 10.1242/jcs.109.6.1555. View

17.

Hiratani I, Leskovar A, Gilbert D . Differentiation-induced replication-timing changes are restricted to AT-rich/long interspersed nuclear element (LINE)-rich isochores. Proc Natl Acad Sci U S A. 2004; 101(48):16861-6. PMC: 534734. DOI: 10.1073/pnas.0406687101. View

18.

Woodward A, Gohler T, Luciani M, Oehlmann M, Ge X, Gartner A . Excess Mcm2-7 license dormant origins of replication that can be used under conditions of replicative stress. J Cell Biol. 2006; 173(5):673-83. PMC: 2063885. DOI: 10.1083/jcb.200602108. View

19.

Wu J, Gilbert D . A distinct G1 step required to specify the Chinese hamster DHFR replication origin. Science. 1996; 271(5253):1270-2. DOI: 10.1126/science.271.5253.1270. View

20.

Mahbubani H, Chong J, Chevalier S, Thommes P, J Blow J . Cell cycle regulation of the replication licensing system: involvement of a Cdk-dependent inhibitor. J Cell Biol. 1997; 136(1):125-35. PMC: 2132454. DOI: 10.1083/jcb.136.1.125. View