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Current Genetics

, Volume 65, Issue 2, pp 429–434 | Cite as

ChECing out Rif1 action in freely cycling cells

  • Lukas Hafner
  • David Shore
  • Stefano MattarocciEmail author
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Abstract

In buddying yeast, like all eukaryotes examined so far, DNA replication is under temporal control, such that some origins fire early and some late during S phase. This replication timing program is established in G1 phase, where chromatin states are thought to prevent binding of key-limiting initiation factors at late-firing origins. Although many factors are involved in replication initiation, a new player, Rif1, has recently entered the scene, with a spate of papers revealing a global role for the protein in the control of replication initiation timing from yeasts to humans. Since budding yeast Rif1 was known to bind only to telomeric and silent mating loci regions, it remained controversial whether Rif1 acts directly at replication origins or instead influences origin activity indirectly. In this perspective, we discuss our recent finding that Rif1 binds directly to the replication origins that it controls. In this study, we also found that Rif1’s regulatory activity at origins is best revealed by an assay (sort-seq) that measures replication in unperturbed, freely cycling cultures, as opposed to commonly used protocols in which cells are first blocked in the G1 phase of the cell cycle by mating pheromone, then released into a synchronous S phase. Finally, we discuss how the sequestration of Rif1 at telomeres, through an interaction with the arrays of Rap1 molecules bound there, plays an important role in limiting Rif1’s action primarily to telomere-proximal replication origins.

Keywords

Chromatin endogenous cleavage (ChEC) DNA replication origins DNA replication timing Rap1 Rif1 

Notes

Acknowledgements

We thank Bernard Bollignan for useful comments and Nicolas Roggli for expert assistance with graphics and artwork. This study was supported by Grants from the Swiss National Science Foundation (to DS), and funds provided by the Republic and Canton of Geneva (to DS). LH was supported by an “Excellence Masters” fellowship from the University of Geneva.

References

  1. Adams IR, McLaren A (2004) Identification and characterisation of mRif1: a mouse telomere-associated protein highly expressed in germ cells and embryo-derived pluripotent stem cells. Dev Dyn 229:733–744.  https://doi.org/10.1002/dvdy.10471 CrossRefGoogle Scholar
  2. Bianchi A, Shore D (2007a) Early replication of short telomeres in. Budding Yeast Cell 128:1051–1062Google Scholar
  3. Bianchi A, Shore D (2007b) Increased association of telomerase with short telomeres. Yeast Genes Dev 21:1726–1730.  https://doi.org/10.1101/gad.438907 CrossRefGoogle Scholar
  4. Cannon JF (2010) Function of protein phosphatase-1, Glc7, in Saccharomyces cerevisiae. Adv Appl Microbiol 73:27–59.  https://doi.org/10.1016/S0065-2164(10)73002-1 CrossRefGoogle Scholar
  5. Cornacchia D et al (2012) Mouse Rif1 is a key regulator of the replication-timing programme in mammalian cells. EMBO J 31:3678–3690.  https://doi.org/10.1038/emboj.2012.214 CrossRefGoogle Scholar
  6. Dave A, Cooley C, Garg M, Bianchi A (2014) Protein phosphatase 1 recruitment by Rif1 regulates DNA replication origin firing by counteracting DDK. Act Cell Rep 7:53–61.  https://doi.org/10.1016/j.celrep.2014.02.019 CrossRefGoogle Scholar
  7. Fontana GA, Reinert JK, Thoma NH, Rass U (2018) Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks. Microb Cell 5:327–343.  https://doi.org/10.15698/mic2018.07.639 CrossRefGoogle Scholar
  8. Hafner L et al (2018) Rif1 binding and control of chromosome-internal DNA replication origins is limited by telomere. Sequestration Cell Rep 23:983–992.  https://doi.org/10.1016/j.celrep.2018.03.113 CrossRefGoogle Scholar
  9. Harari Y, Kupiec M (2018) Mec1(ATR) is needed for extensive telomere elongation in response to ethanol in yeast. Curr Genet 64:223–234.  https://doi.org/10.1007/s00294-017-0728-1 CrossRefGoogle Scholar
  10. Hardy CF, Sussel L, Shore D (1992) A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation. Genes Dev 6:801–814CrossRefGoogle Scholar
  11. Hayano M, Kanoh Y, Matsumoto S, Renard-Guillet C, Shirahige K, Masai H (2012) Rif1 is a global regulator of timing of replication origin firing in fission yeast. Genes Dev 26:137–150.  https://doi.org/10.1101/gad.178491.111 CrossRefGoogle Scholar
  12. Hiraga S et al (2014) Rif1 controls DNA replication by directing protein phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex. Genes Dev 28:372–383.  https://doi.org/10.1101/gad.231258.113 CrossRefGoogle Scholar
  13. Hiraga SI, Monerawela C, Katou Y, Shaw S, Clark KR, Shirahige K, Donaldson AD (2018) Budding yeast Rif1 binds to replication origins and protects DNA at blocked replication forks EMBO Rep.  https://doi.org/10.15252/embr.201846222 Google Scholar
  14. Kanoh J, Ishikawa F (2001) spRap1 and spRif1, recruited to telomeres by Taz1, are essential for telomere function in fission yeast. Curr Biol 11:1624–1630CrossRefGoogle Scholar
  15. Kanoh Y et al (2015) Rif1 binds to G quadruplexes and suppresses replication over long distances. Nat Struct Mol Biol 22:889–897.  https://doi.org/10.1038/nsmb.3102 CrossRefGoogle Scholar
  16. Knight B et al (2014) Two distinct promoter architectures centered on dynamic nucleosomes control ribosomal protein gene transcription. Genes Dev 28:1695–1709.  https://doi.org/10.1101/gad.244434.114 CrossRefGoogle Scholar
  17. Lian HY et al (2011) The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation. Mol Biol Cell 22:1753–1765.  https://doi.org/10.1091/mbc.E10-06-0549 CrossRefGoogle Scholar
  18. Lieb JD, Liu X, Botstein D, Brown PO (2001) Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA. Assoc Nat Genet 28:327–334.  https://doi.org/10.1038/ng569 CrossRefGoogle Scholar
  19. Maillet L, Boscheron C, Gotta M, Marcand S, Gilson E, Gasser SM (1996) Evidence for silencing compartments within the yeast nucleus: a role for telomere proximity and Sir protein concentration in silencer-mediated repression. Genes Dev 10:1796–1811CrossRefGoogle Scholar
  20. Mantiero D, Mackenzie A, Donaldson A, Zegerman P (2011) Limiting replication initiation factors execute the temporal programme of origin firing in budding yeast. EMBO J 30:4805–4814.  https://doi.org/10.1038/emboj.2011.404 CrossRefGoogle Scholar
  21. Marcand S, Buck SW, Moretti P, Gilson E, Shore D (1996) Silencing of genes at nontelomeric sites in yeast is controlled by sequestration of silencing factors at telomeres by Rap 1 protein. Genes Dev 10:1297–1309CrossRefGoogle Scholar
  22. Martina M, Bonetti D, Villa M, Lucchini G, Longhese MP (2014) Saccharomyces cerevisiae Rif1 cooperates with MRX-Sae2 in promoting DNA-end resection. EMBO Rep 15:695–704.  https://doi.org/10.1002/embr.201338338 Google Scholar
  23. Mattarocci S et al (2014) Rif1 controls DNA replication timing in yeast through the PP1 phosphatase Glc7. Cell Rep 7:62–69.  https://doi.org/10.1016/j.celrep.2014.03.010 CrossRefGoogle Scholar
  24. Mattarocci S, Hafner L, Lezaja A, Shyian M, Shore D (2016) Rif1: a conserved regulator of DNA replication and repair hijacked by telomeres in. Yeasts Front Genet 7:45.  https://doi.org/10.3389/fgene.2016.00045 Google Scholar
  25. Mattarocci S et al (2017) Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends Nat. Struct Mol Biol 24:588–595.  https://doi.org/10.1038/nsmb.3420 CrossRefGoogle Scholar
  26. Mishra K, Shore D (1999) Yeast Ku protein plays a direct role in telomeric silencing and counteracts inhibition by rif proteins. Curr Biol 9:1123–1126CrossRefGoogle Scholar
  27. Muller CA et al (2014) The dynamics of genome replication using deep sequencing. Nucleic Acids Res 42:e3.  https://doi.org/10.1093/nar/gkt878 CrossRefGoogle Scholar
  28. Peace JM, Ter-Zakarian A, Aparicio OM (2014) Rif1 regulates initiation timing of late replication origins throughout the S. cerevisiae genome. PLoS One 9:e98501.  https://doi.org/10.1371/journal.pone.0098501 CrossRefGoogle Scholar
  29. Perez-Romero CA, Lalonde M, Chartrand P, Cusanelli E (2018) Induction and relocalization of telomeric repeat-containing RNAs during diauxic shift in budding yeast. Curr Genet 64:1117–1127.  https://doi.org/10.1007/s00294-018-0829-5 CrossRefGoogle Scholar
  30. Pope BD, Gilbert DM (2013) The replication domain model: regulating replicon firing in the context of large-scale chromosome architecture. J Mol Biol 425:4690–4695.  https://doi.org/10.1016/j.jmb.2013.04.014 CrossRefGoogle Scholar
  31. Pope PA, Pryciak PM (2013) Functional overlap among distinct G1/S inhibitory pathways allows robust G1 arrest by yeast mating pheromones. Mol Biol Cell 24:3675–3688.  https://doi.org/10.1091/mbc.E13-07-0373 CrossRefGoogle Scholar
  32. Poschke H, Dees M, Chang M, Amberkar S, Kaderali L, Rothstein R, Luke B (2012) Rif2 promotes a telomere fold-back structure through Rpd3L recruitment in budding yeast. PLoS Genet 8:e1002960.  https://doi.org/10.1371/journal.pgen.1002960 CrossRefGoogle Scholar
  33. Raghuraman MK, Brewer BJ, Fangman WL (1997) Cell cycle-dependent establishment of a late. Replication Program Sci 276:806–809Google Scholar
  34. Raghuraman MK et al (2001) Replication dynamics of the yeast genome. Science 294:115–121.  https://doi.org/10.1126/science.294.5540.115 CrossRefGoogle Scholar
  35. Rhind N, Gilbert DM (2013) DNA replication timing. Cold Spring Harb Perspect Biol 5(8):a010132.  https://doi.org/10.1101/cshperspect.a010132 CrossRefGoogle Scholar
  36. Sabourin M, Tuzon CT, Zakian VA (2007) Telomerase and Tel1p preferentially associate with short telomeres in S. cerevisiae. Mol Cell 27:550–561.  https://doi.org/10.1016/j.molcel.2007.07.016 CrossRefGoogle Scholar
  37. Schmid M, Durussel T, Laemmli UK (2004) ChIC and ChEC; genomic mapping of chromatin proteins. Mol Cell 16:147–157Google Scholar
  38. Shi T et al (2013) Rif1 and Rif2 shape telomere function and architecture through multivalent Rap1 interactions. Cell 153:1340–1353.  https://doi.org/10.1016/j.cell.2013.05.007 CrossRefGoogle Scholar
  39. Shyian M et al (2016) Budding yeast Rif1 controls genome integrity by inhibiting rDNA. Replication PLoS Genet 12:e1006414.  https://doi.org/10.1371/journal.pgen.1006414 CrossRefGoogle Scholar
  40. Silverman J, Takai H, Buonomo SB, Eisenhaber F, de Lange T (2004) Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint. Genes Dev 18:2108–2119.  https://doi.org/10.1101/gad.1216004 CrossRefGoogle Scholar
  41. Tomita K (2018) How long does telomerase extend telomeres? Regulation of telomerase release and telomere length homeostasis. Curr Genet.  https://doi.org/10.1007/s00294-018-0836-6 Google Scholar
  42. Wotton D, Shore D (1997) A novel Rap1p-interacting factor, Rif2p, cooperates with Rif1p to regulate telomere length in Saccharomyces cerevisiae. Genes Dev 11:748–760CrossRefGoogle Scholar
  43. Xu L, Blackburn EH (2004) Human Rif1 protein binds aberrant telomeres and aligns along anaphase midzone microtubules. J Cell Biol 167:819–830.  https://doi.org/10.1083/jcb.200408181 CrossRefGoogle Scholar
  44. Yamazaki S, Ishii A, Kanoh Y, Oda M, Nishito Y, Masai H (2012) Rif1 regulates the replication timing domains on the human genome. EMBO J 31:3667–3677.  https://doi.org/10.1038/emboj.2012.180 CrossRefGoogle Scholar
  45. Zentner GE, Kasinathan S, Xin B, Rohs R, Henikoff S (2015) ChEC-seq kinetics discriminates transcription factor binding sites by DNA sequence and shape in vivo. Nat Commun 6:8733.  https://doi.org/10.1038/ncomms9733 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Molecular BiologyUniversity of GenevaGenevaSwitzerland
  2. 2.Institute of Genetics and Genomics of Geneva (iGE3)GenevaSwitzerland
  3. 3.Sorbonne Université, PSL Research University, CNRS, UMR8226, Institut de Biologie Physico-Chimique, Laboratoire de Biologie Moléculaire et Cellulaire des EucaryotesParisFrance
  4. 4.Biology of Infection UnitInstitut PasteurParisFrance

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