Mouse Rif1 is a Key Regulator of the Replication-timing Programme in Mammalian Cells

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2012 Aug 2

PMID 22850673

Citations 140

Authors

Daniela Cornacchia

Vishnu Dileep

Jean-Pierre Quivy

Rossana Foti

Federico Tili

Rachel Santarella-Mellwig

Claude Antony

Genevieve Almouzni

David M Gilbert

Sara B C Buonomo

Affiliations

Soon will be listed here.

Abstract

The eukaryotic genome is replicated according to a specific spatio-temporal programme. However, little is known about both its molecular control and biological significance. Here, we identify mouse Rif1 as a key player in the regulation of DNA replication timing. We show that Rif1 deficiency in primary cells results in an unprecedented global alteration of the temporal order of replication. This effect takes place already in the first S-phase after Rif1 deletion and is neither accompanied by alterations in the transcriptional landscape nor by major changes in the biochemical identity of constitutive heterochromatin. In addition, Rif1 deficiency leads to both defective G1/S transition and chromatin re-organization after DNA replication. Together, these data offer a novel insight into the global regulation and biological significance of the replication-timing programme in mammalian cells.

Citing Articles

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References

Knott S, Peace J, Ostrow A, Gan Y, Rex A, Viggiani C . Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Cell. 2012; 148(1-2):99-111. PMC: 3266545. DOI: 10.1016/j.cell.2011.12.012. View

Quivy J, Gerard A, Cook A, Roche D, Almouzni G . The HP1-p150/CAF-1 interaction is required for pericentric heterochromatin replication and S-phase progression in mouse cells. Nat Struct Mol Biol. 2009; 15(9):972-9. DOI: 10.1038/nsmb.1470. 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

Bahtz R, Seidler J, Arnold M, Haselmann-Weiss U, Antony C, Lehmann W . GCP6 is a substrate of Plk4 and required for centriole duplication. J Cell Sci. 2012; 125(Pt 2):486-96. DOI: 10.1242/jcs.093930. View

Waga S, Hannon G, Beach D, Stillman B . The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature. 1994; 369(6481):574-8. DOI: 10.1038/369574a0. View

Flores-Rozas H, Kelman Z, Dean F, Pan Z, Harper J, Elledge S . Cdk-interacting protein 1 directly binds with proliferating cell nuclear antigen and inhibits DNA replication catalyzed by the DNA polymerase delta holoenzyme. Proc Natl Acad Sci U S A. 1994; 91(18):8655-9. PMC: 44665. DOI: 10.1073/pnas.91.18.8655. View

Lian H, Robertson E, Hiraga S, Alvino G, Collingwood D, McCune H . The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation. Mol Biol Cell. 2011; 22(10):1753-65. PMC: 3093326. DOI: 10.1091/mbc.E10-06-0549. View

Hardy C, Sussel L, Shore D . A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation. Genes Dev. 1992; 6(5):801-14. DOI: 10.1101/gad.6.5.801. View

Sobel R, Cook R, Perry C, Annunziato A, Allis C . Conservation of deposition-related acetylation sites in newly synthesized histones H3 and H4. Proc Natl Acad Sci U S A. 1995; 92(4):1237-41. PMC: 42674. DOI: 10.1073/pnas.92.4.1237. View

10.

Park S, Patterson E, Cobb J, Audhya A, Gartenberg M, Fox C . Palmitoylation controls the dynamics of budding-yeast heterochromatin via the telomere-binding protein Rif1. Proc Natl Acad Sci U S A. 2011; 108(35):14572-7. PMC: 3167557. DOI: 10.1073/pnas.1105262108. View

11.

Gallardo F, Laterreur N, Cusanelli E, Ouenzar F, Querido E, Wellinger R . Live cell imaging of telomerase RNA dynamics reveals cell cycle-dependent clustering of telomerase at elongating telomeres. Mol Cell. 2011; 44(5):819-27. DOI: 10.1016/j.molcel.2011.09.020. View

12.

Xu L, Blackburn E . Human Rif1 protein binds aberrant telomeres and aligns along anaphase midzone microtubules. J Cell Biol. 2004; 167(5):819-30. PMC: 2172464. DOI: 10.1083/jcb.200408181. View

13.

Dimitrova D, Gilbert D . DNA replication and nuclear organization: prospects for a soluble in vitro system. Crit Rev Eukaryot Gene Expr. 2000; 9(3-4):353-61. DOI: 10.1615/critreveukargeneexpr.v9.i3-4.200. View

14.

Chubb J, Boyle S, Perry P, Bickmore W . Chromatin motion is constrained by association with nuclear compartments in human cells. Curr Biol. 2002; 12(6):439-45. DOI: 10.1016/s0960-9822(02)00695-4. View

15.

Mantiero D, MacKenzie A, Donaldson A, Zegerman P . Limiting replication initiation factors execute the temporal programme of origin firing in budding yeast. EMBO J. 2011; 30(23):4805-14. PMC: 3243606. DOI: 10.1038/emboj.2011.404. View

16.

Hiratani I, Takebayashi S, Lu J, Gilbert D . Replication timing and transcriptional control: beyond cause and effect--part II. Curr Opin Genet Dev. 2009; 19(2):142-9. PMC: 2677117. DOI: 10.1016/j.gde.2009.02.002. View

17.

Ward I, Minn K, van Deursen J, Chen J . p53 Binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice. Mol Cell Biol. 2003; 23(7):2556-63. PMC: 150747. DOI: 10.1128/MCB.23.7.2556-2563.2003. View

18.

De S, Michor F . DNA replication timing and long-range DNA interactions predict mutational landscapes of cancer genomes. Nat Biotechnol. 2011; 29(12):1103-8. PMC: 3923360. DOI: 10.1038/nbt.2030. View

19.

Wu R, Singh P, Gilbert D . Uncoupling global and fine-tuning replication timing determinants for mouse pericentric heterochromatin. J Cell Biol. 2006; 174(2):185-94. PMC: 2064179. DOI: 10.1083/jcb.200601113. View

20.

Gilbert D . Nuclear position leaves its mark on replication timing. J Cell Biol. 2001; 152(2):F11-5. PMC: 1255920. DOI: 10.1083/jcb.152.2.f11. View