Advertisement

Current Genetics

, Volume 55, Issue 4, pp 357–363 | Cite as

The dual role of autonomously replicating sequences as origins of replication and as silencers

  • Muhammad Attiq Rehman
  • Krassimir YankulovEmail author
Review

Abstract

Autonomously replicating sequences (ARSs) in Saccharomyces cerevisiae have been extensively characterized as both origins of DNA replication and as chromatin repressors/silencers. It has been conclusively shown that the origin and the silencer activities of ARS are substantially, but not entirely interchangeable and that they are modulated by position effects and chromatin environment. It remains unclear how these two quite divergent functions of ARS co-exist. This perspective focuses on recent advances, which have shown that slight differences in ARSs can modulate their affinity for origin recognition complex and their activity as silencers or origins.

Keywords

ARS DNA replication Gene silencing ORC 

Abbreviations

ARS

Autonomously replicating sequence

ACS

ARS consensus sequence

SIR

Silent information regulator

ORC

Origin recognition complex

MCM

Mini-chromosome maintenance

pre-RC

pre-replicative complex

Notes

Acknowledgments

M.A.R. and K.Y. are supported by a grant from NSERC, Canada.

References

  1. Blow JJ, Dutta A (2005) Preventing re-replication of chromosomal DNA. Nat Rev Mol Cell Biol 6:476–486. doi: 10.1038/nrm1663 PubMedCrossRefGoogle Scholar
  2. Broach JR, Li YY, Feldman J, Jayaram M, Abraham J, Nasmyth KA, Hicks JB (1983) Localization and sequence analysis of yeast origins of DNA replication. Cold Spring Harb Symp Quant Biol 47 Pt 2: 1165–1173Google Scholar
  3. Casey L, Patterson EE, Muller U, Fox CA (2008) Conversion of a replication origin to a silencer through a pathway shared by a Forkhead transcription factor and an S phase cyclin. Mol Biol Cell 19:608–622. doi: 10.1091/mbc.E07-04-0323 PubMedCrossRefGoogle Scholar
  4. Chan CS, Tye BK (1980) Autonomously replicating sequences in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 77:6329–6333PubMedCrossRefGoogle Scholar
  5. Chang F, Theis JF, Miller J, Nieduszynski CA, Newlon CS, Weinreich M (2008) Analysis of chromosome III replicators reveals an unusual structure for the ARS318 silencer origin and a conserved WTW sequence within the origin recognition complex binding site. Mol Cell Biol 28:5071–5081. doi: 10.1128/MCB.00206-08 PubMedCrossRefGoogle Scholar
  6. Chastain PD 2nd, Bowers JL, Lee DG, Bell SP, Griffith JD (2004) Mapping subunit location on the Saccharomyces cerevisiae origin recognition complex free and bound to DNA using a novel nanoscale biopointer. J Biol Chem 279:36354–36362. doi: 10.1074/jbc.M403501200 PubMedCrossRefGoogle Scholar
  7. Chen Z, Speck C, Wendel P, Tang C, Stillman B, Li H (2008) The architecture of the DNA replication origin recognition complex in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 105:10326–10331. doi: 10.1073/pnas.0803829105 PubMedCrossRefGoogle Scholar
  8. Ehrenhofer-Murray AE, Rivier DH, Rine J (1997) The role of Sas2, an acetyltransferase homologue of Saccharomyces cerevisiae, in silencing and ORC function. Genetics 145:923–934PubMedGoogle Scholar
  9. Ehrenhofer-Murray AE, Kamakaka RT, Rine J (1999) A role for the replication proteins PCNA, RF-C, polymerase epsilon and Cdc45 in transcriptional silencing in Saccharomyces cerevisiae. Genetics 153:1171–1182PubMedGoogle Scholar
  10. Eisenberg S, Civalier C, Tye BK (1988) Specific interaction between a Saccharomyces cerevisiae protein and a DNA element associated with certain autonomously replicating sequences. Proc Natl Acad Sci USA 85:743–746PubMedCrossRefGoogle Scholar
  11. Feng W, Collingwood D, Boeck ME, Fox LA, Alvino GM, Fangman WL, Raghuraman MK, Brewer BJ (2006) Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication. Nat Cell Biol 8:148–155. doi: 10.1038/ncb1358 PubMedCrossRefGoogle Scholar
  12. Fourel G, Revardel E, Koering CE, Gilson E (1999) Cohabitation of insulators and silencing elements in yeast subtelomeric regions. EMBO J 18:2522–2537. doi: 10.1093/emboj/18.9.2522 PubMedCrossRefGoogle Scholar
  13. Fourel G, Lebrun E, Gilson E (2002) Protosilencers as building blocks for heterochromatin. Bioessays 24:828–835. doi: 10.1002/bies.10139 PubMedCrossRefGoogle Scholar
  14. Fox CA, Loo S, Dillin A, Rine J (1995) The origin recognition complex has essential functions in transcriptional silencing and chromosomal replication. Genes Dev 9:911–924PubMedCrossRefGoogle Scholar
  15. Huang RY, Kowalski D (1996) Multiple DNA elements in ARS305 determine replication origin activity in a yeast chromosome. Nucleic Acids Res 24:816–823. doi: 5e0780[pii] PubMedCrossRefGoogle Scholar
  16. Kearsey S (1983) Analysis of sequences conferring autonomous replication in baker’s yeast. EMBO J 2:1571–1575PubMedGoogle Scholar
  17. Kimmerly W, Buchman A, Kornberg R, Rine J (1988) Roles of two DNA-binding factors in replication, segregation and transcriptional repression mediated by a yeast silencer. EMBO J 7:2241–2253PubMedGoogle Scholar
  18. Lee DG, Bell SP (1997) Architecture of the yeast origin recognition complex bound to origins of DNA replication. Mol Cell Biol 17:7159–7168PubMedGoogle Scholar
  19. Lee DG, Makhov AM, Klemm RD, Griffith JD, Bell SP (2000) Regulation of origin recognition complex conformation and ATPase activity: differential effects of single-stranded and double-stranded DNA binding. EMBO J 19:4774–4782. doi: 10.1093/emboj/19.17.4774 PubMedCrossRefGoogle Scholar
  20. Li R, Yu DS, Tanaka M, Zheng L, Berger SL, Stillman B (1998) Activation of chromosomal DNA replication in Saccharomyces cerevisiae by acidic transcriptional activation domains. Mol Cell Biol 18:1296–1302PubMedGoogle Scholar
  21. Liachko I, Tye BK (2009) Mcm10 mediates the interaction between DNA replication and silencing machineries. Genetics 181:379–391. doi: 10.1534/genetics.108.099101 PubMedCrossRefGoogle Scholar
  22. Marahrens Y, Stillman B (1992) A yeast chromosomal origin of DNA replication defined by multiple functional elements. Science 255:817–823PubMedCrossRefGoogle Scholar
  23. McConnell KH, Muller P, Fox CA (2006) Tolerance of Sir1p/origin recognition complex-dependent silencing for enhanced origin firing at HMRa. Mol Cell Biol 26:1955–1966. doi: 10.1128/MCB.26.5.1955-1966.2006 PubMedCrossRefGoogle Scholar
  24. McNally FJ, Rine J (1991) A synthetic silencer mediates SIR-dependent functions in Saccharomyces cerevisiae. Mol Cell Biol 11:5648–5659PubMedGoogle Scholar
  25. Mizushima T, Takahashi N, Stillman B (2000) Cdc6p modulates the structure and DNA binding activity of the origin recognition complex in vitro. Genes Dev 14:1631–1641PubMedGoogle Scholar
  26. Nguyen VQ, Co C, Li JJ (2001) Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature 411:1068–1073. doi: 10.1038/3508260035082600[pii] PubMedCrossRefGoogle Scholar
  27. Palacios DeBeer MA, Fox CA (1999) A role for a replicator dominance mechanism in silencing. EMBO J 18:3808–3819. doi: 10.1093/emboj/18.13.3808 PubMedCrossRefGoogle Scholar
  28. Palacios DeBeer MA, Muller U, Fox CA (2003) Differential DNA affinity specifies roles for the origin recognition complex in budding yeast heterochromatin. Genes Dev 17:1817–1822. doi: 10.1101/gad.109670317/15/1817 PubMedCrossRefGoogle Scholar
  29. Pasero P, Bensimon A, Schwob E (2002) Single-molecule analysis reveals clustering and epigenetic regulation of replication origins at the yeast rDNA locus. Genes Dev 16:2479–2484. doi: 10.1101/gad.232902 PubMedCrossRefGoogle Scholar
  30. Pryde FE, Louis EJ (1999) Limitations of silencing at native yeast telomeres. EMBO J 18:2538–2550. doi: 10.1093/emboj/18.9.2538 PubMedCrossRefGoogle Scholar
  31. Raghuraman MK, Winzeler EA, Collingwood D, Hunt S, Wodicka L, Conway A, Lockhart DJ, Davis RW, Brewer BJ, Fangman WL (2001) Replication dynamics of the yeast genome. Science 294:115–121. doi: 10.1126/science.294.5540.115294/5540/115[pii] PubMedCrossRefGoogle Scholar
  32. Ramachandran L, Burhans DT, Laun P, Wang J, Liang P, Weinberger M, Wissing S, Jarolim S, Suter B, Madeo F, Breitenbach M, Burhans WC (2006) Evidence for ORC-dependent repression of budding yeast genes induced by starvation and other stresses. FEMS Yeast Res 6:763–776. doi: 10.1111/j.1567-1364.2006.00077.x PubMedCrossRefGoogle Scholar
  33. Rao H, Stillman B (1995) The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators. Proc Natl Acad Sci USA 92:2224–2228PubMedCrossRefGoogle Scholar
  34. Rehman MA, Fourel G, Mathews A, Ramdin D, Espinosa M, Gilson E, Yankulov K (2006) Differential requirement of DNA replication factors for subtelomeric ARS consensus sequence protosilencers in Saccharomyces cerevisiae. Genetics 174:1801–1810. doi: 10.1534/genetics.106.063446 PubMedCrossRefGoogle Scholar
  35. Rehman MA, Wang D, Fourel G, Gilson E, Yankulov K (2009) Subtelomeric ACS-containing proto-silencers act as antisilencers in replication factors mutants in Saccharomyces cerevisiae. Mol Biol Cell 20:631–641. doi: 10.1091/mbc.E08-01-0099 PubMedCrossRefGoogle Scholar
  36. Rusche LN, Kirchmaier AL, Rine J (2003) The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae. Annu Rev Biochem 72:481–516. doi: 10.1146/annurev.biochem.72.121801.161547 PubMedCrossRefGoogle Scholar
  37. Santocanale C, Diffley JF (1998) A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication. Nature 395:615–618. doi: 10.1038/27001 PubMedCrossRefGoogle Scholar
  38. Sharma K, Weinberger M, Huberman JA (2001) Roles for internal and flanking sequences in regulating the activity of mating-type-silencer-associated replication origins in Saccharomyces cerevisiae. Genetics 159:35–45PubMedGoogle Scholar
  39. Stillman B (2005) Origin recognition and the chromosome cycle. FEBS Lett 579:877–884. doi: 10.1016/j.febslet.2004.12.011 PubMedCrossRefGoogle Scholar
  40. Stinchcomb DT, Struhl K, Davis RW (1979) Isolation and characterisation of a yeast chromosomal replicator. Nature 282:39–43PubMedCrossRefGoogle Scholar
  41. Strahl-Bolsinger S, Hecht A, Luo K, Grunstein M (1997) SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast. Genes Dev 11:83–93PubMedCrossRefGoogle Scholar
  42. Vas A, Mok W, Leatherwood J (2001) Control of DNA rereplication via Cdc2 phosphorylation sites in the origin recognition complex. Mol Cell Biol 21:5767–5777PubMedCrossRefGoogle Scholar
  43. Weinreich M, Palacios DeBeer MA, Fox CA (2004) The activities of eukaryotic replication origins in chromatin. Biochim Biophys Acta 1677:142–157. doi: 10.1016/j.bbaexp.2003.11.015 PubMedGoogle Scholar
  44. Wilmes GM, Bell SP (2002) The B2 element of the Saccharomyces cerevisiae ARS1 origin of replication requires specific sequences to facilitate pre-RC formation. Proc Natl Acad Sci USA 99:101–106. doi: 10.1073/pnas.012578499 PubMedCrossRefGoogle Scholar
  45. Wilmes GM, Archambault V, Austin RJ, Jacobson MD, Bell SP, Cross FR (2004) Interaction of the S-phase cyclin Clb5 with an “RXL” docking sequence in the initiator protein Orc6 provides an origin-localized replication control switch. Genes Dev 18:981–991. doi: 10.1101/gad.1202304 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Department of Molecular and Cellular BiologyUniversity of GuelphGuelphCanada
  2. 2.Laboratory of Gene Regulation and DevelopmentNational Institute of Child Health and Human Development, NIHBethesdaUSA

Personalised recommendations