Gene Symbol: RLF2
Description: Rlf2p
Alias: CAC1, Rlf2p
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Driscoll R, Hudson A, Jackson S. Yeast Rtt109 promotes genome stability by acetylating histone H3 on lysine 56. Science. 2007;315:649-52 pubmed
    ..These data establish Rtt109p as a member of a new class of histone acetyltransferases and show that its actions are critical for cell survival in the presence of DNA damage during S phase...
  2. Huang S, Zhou H, Katzmann D, Hochstrasser M, Atanasova E, Zhang Z. Rtt106p is a histone chaperone involved in heterochromatin-mediated silencing. Proc Natl Acad Sci U S A. 2005;102:13410-5 pubmed
    ..Furthermore, Rtt106p interacts with CAF-1 physically through Cac1p. These biochemical and genetic data indicate that Rtt106p is a previously uncharacterized histone chaperone connecting S phase to epigenetic inheritance. ..
  3. Burgess R, Zhou H, Han J, Zhang Z. A role for Gcn5 in replication-coupled nucleosome assembly. Mol Cell. 2010;37:469-80 pubmed publisher
    ..These results demonstrate that Gcn5 regulates RC nucleosome assembly, in part, by promoting H3 association with CAF-1 via H3 acetylation. ..
  4. Enomoto S, McCune Zierath P, Gerami Nejad M, Sanders M, Berman J. RLF2, a subunit of yeast chromatin assembly factor-I, is required for telomeric chromatin function in vivo. Genes Dev. 1997;11:358-70 pubmed
    ..In wild-type cells, epitope-tagged Rlf2p expressed from the GAL10 promoter localizes to the nucleus with a pattern distinct from that of Rap1p, suggesting ..
  5. Li Q, Zhou H, Wurtele H, Davies B, Horazdovsky B, Verreault A, et al. Acetylation of histone H3 lysine 56 regulates replication-coupled nucleosome assembly. Cell. 2008;134:244-55 pubmed publisher
    ..These results reveal a mechanism by which H3K56Ac regulates replication-coupled nucleosome assembly mediated by CAF-1 and Rtt106. ..
  6. Erkmann J, Kaufman P. A negatively charged residue in place of histone H3K56 supports chromatin assembly factor association but not genotoxic stress resistance. DNA Repair (Amst). 2009;8:1371-9 pubmed publisher
    ..Our studies therefore emphasize how H3 K56ac not only promotes chromatin assembly but also leads to chromosomal malfunction if not removed following histone deposition. ..
  7. Kaufman P, Kobayashi R, Stillman B. Ultraviolet radiation sensitivity and reduction of telomeric silencing in Saccharomyces cerevisiae cells lacking chromatin assembly factor-I. Genes Dev. 1997;11:345-57 pubmed
    ..The CAC1 and CAC2 (chromatin assembly complex) genes encode proteins similar to the p150 and p60 subunits of human CAF-I, ..
  8. Tyler J, Adams C, Chen S, Kobayashi R, Kamakaka R, Kadonaga J. The RCAF complex mediates chromatin assembly during DNA replication and repair. Nature. 1999;402:555-60 pubmed
  9. Su D, Hu Q, Li Q, Thompson J, Cui G, Fazly A, et al. Structural basis for recognition of H3K56-acetylated histone H3-H4 by the chaperone Rtt106. Nature. 2012;483:104-7 pubmed publisher
    ..We show that the Rtt106-(H3-H4)(2) interaction is important for gene silencing and the DNA damage response. ..

More Information


  1. Kim J, Haber J. Chromatin assembly factors Asf1 and CAF-1 have overlapping roles in deactivating the DNA damage checkpoint when DNA repair is complete. Proc Natl Acad Sci U S A. 2009;106:1151-6 pubmed publisher
    ..DSB repair or formation of gamma-H2AX does not depend on either the CAF-1 protein, Cac1, or Asf1...
  2. Zhang Z, Shibahara K, Stillman B. PCNA connects DNA replication to epigenetic inheritance in yeast. Nature. 2000;408:221-5 pubmed
    ..Thus, PCNA participates in inheritance of both DNA and epigenetic chromatin structures during the S phase of the cell cycle, the latter by at least two mechanisms. ..
  3. Myung K, Pennaneach V, Kats E, Kolodner R. Saccharomyces cerevisiae chromatin-assembly factors that act during DNA replication function in the maintenance of genome stability. Proc Natl Acad Sci U S A. 2003;100:6640-5 pubmed
    ..These results indicate that coupling of chromatin assembly to DNA replication and DNA repair is critical to maintaining genome stability. ..
  4. Gunjan A, Verreault A. A Rad53 kinase-dependent surveillance mechanism that regulates histone protein levels in S. cerevisiae. Cell. 2003;115:537-49 pubmed
    ..Our results argue that Rad53 contributes to genome stability independently of Mec1 by preventing the damaging effects of excess histones both during normal cell cycle progression and in response to DNA damage. ..
  5. Krawitz D, Kama T, Kaufman P. Chromatin assembly factor I mutants defective for PCNA binding require Asf1/Hir proteins for silencing. Mol Cell Biol. 2002;22:614-25 pubmed
    ..Saccharomyces cerevisiae mutants lacking CAF-I subunit genes (CAC1 to CAC3) display reduced heterochromatic gene silencing...
  6. Kaufman P, Cohen J, Osley M. Hir proteins are required for position-dependent gene silencing in Saccharomyces cerevisiae in the absence of chromatin assembly factor I. Mol Cell Biol. 1998;18:4793-806 pubmed
  7. Meijsing S, Ehrenhofer Murray A. The silencing complex SAS-I links histone acetylation to the assembly of repressed chromatin by CAF-I and Asf1 in Saccharomyces cerevisiae. Genes Dev. 2001;15:3169-82 pubmed
    ..In this study, the MYST family acetyltransferase Sas2 was found to interact with Cac1, the largest subunit of Saccharomyces cerevisiae chromatin assembly factor-I (CAF-I), and with the nucleosome ..
  8. Kats E, Albuquerque C, Zhou H, Kolodner R. Checkpoint functions are required for normal S-phase progression in Saccharomyces cerevisiae RCAF- and CAF-I-defective mutants. Proc Natl Acad Sci U S A. 2006;103:3710-5 pubmed
    ..FACS analysis of mutants lacking Asf1 or Cac1 as well as various checkpoint proteins indicated that normal rates of S-phase progression in asf1 mutants have a ..
  9. Rossmann M, Luo W, Tsaponina O, Chabes A, Stillman B. A common telomeric gene silencing assay is affected by nucleotide metabolism. Mol Cell. 2011;42:127-36 pubmed publisher
    ..We conclude that metabolic changes caused by the drug employed and certain mutants being studied are incompatible with the use of certain prototrophic markers for TPEV. ..
  10. English C, Adkins M, Carson J, Churchill M, Tyler J. Structural basis for the histone chaperone activity of Asf1. Cell. 2006;127:495-508 pubmed
    ..The Asf1-H3/H4 structure suggests a "strand-capture" mechanism whereby the H4 tail acts as a lever to facilitate chromatin disassembly/assembly that may be used ubiquitously by histone chaperones. ..
  11. Masumoto H, Hawke D, Kobayashi R, Verreault A. A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response. Nature. 2005;436:294-8 pubmed
    ..We suggest that the acetylation of histone H3 K56 creates a favourable chromatin environment for DNA repair and that a key component of the DNA damage response is to preserve this acetylation. ..
  12. Smith J, Caputo E, Boeke J. A genetic screen for ribosomal DNA silencing defects identifies multiple DNA replication and chromatin-modulating factors. Mol Cell Biol. 1999;19:3184-97 pubmed
    ..Mutations in rpd3 also restored mating competence selectively to sir3Delta MATalpha strains, suggesting restoration of silencing at HMR in a sir3 mutant background. ..
  13. Sharp J, Fouts E, Krawitz D, Kaufman P. Yeast histone deposition protein Asf1p requires Hir proteins and PCNA for heterochromatic silencing. Curr Biol. 2001;11:463-73 pubmed
    ..the four HIR genes and nucleosome assembly proteins Asf1p and chromatin assembly factor I (CAF-I, encoded by the CAC1-3 genes)...
  14. Lewis L, Karthikeyan G, Cassiano J, Resnick M. Reduction of nucleosome assembly during new DNA synthesis impairs both major pathways of double-strand break repair. Nucleic Acids Res. 2005;33:4928-39 pubmed
    Assembly of new chromatin during S phase requires the histone chaperone complexes CAF-1 (Cac2p, Msi1p and Rlf2p) and RCAF (Asf1p plus acetylated histones H3 and H4)...
  15. Vishnoi N, Flaherty K, Hancock L, Ferreira M, Amin A, Prochasson P. Separation-of-function mutation in HPC2, a member of the HIR complex in S. cerevisiae, results in derepression of the histone genes but does not confer cryptic TATA phenotypes. Biochim Biophys Acta. 2011;1809:557-66 pubmed publisher
    ..This is the first direct demonstration that a separation-of-function mutation exists within the HIR complex. ..
  16. Harkness T, Arnason T, Legrand C, Pisclevich M, Davies G, Turner E. Contribution of CAF-I to anaphase-promoting-complex-mediated mitotic chromatin assembly in Saccharomyces cerevisiae. Eukaryot Cell. 2005;4:673-84 pubmed
    ..When present in multiple copies, the individual CAF-I genes, CAC1, CAC2, and MSI1, suppress apc5(CA) phenotypes in a CAF-1- and Asf1p-independent manner...
  17. Jeffery D, Kakusho N, You Z, Gharib M, Wyse B, Drury E, et al. CDC28 phosphorylates Cac1p and regulates the association of chromatin assembly factor I with chromatin. Cell Cycle. 2015;14:74-85 pubmed publisher
    ..Hence, we implicate CDC28 in the regulation of chromatin reassembly during DNA replication. These findings provide novel mechanistic insights on the links between cell-cycle regulation, DNA replication and chromatin reassembly. ..
  18. Zhou H, Madden B, Muddiman D, Zhang Z. Chromatin assembly factor 1 interacts with histone H3 methylated at lysine 79 in the processes of epigenetic silencing and DNA repair. Biochemistry. 2006;45:2852-61 pubmed
    ..Together, these data indicate that CAF-1 interacts with H3 methylated at lysine 79 during the processes of epigenetic silencing and DNA repair. ..
  19. Miele A, Bystricky K, Dekker J. Yeast silent mating type loci form heterochromatic clusters through silencer protein-dependent long-range interactions. PLoS Genet. 2009;5:e1000478 pubmed publisher
  20. Singh R, Kabbaj M, Paik J, Gunjan A. Histone levels are regulated by phosphorylation and ubiquitylation-dependent proteolysis. Nat Cell Biol. 2009;11:925-33 pubmed publisher
    ..Regulated histone proteolysis has major implications for the maintenance of epigenetic marks on chromatin, genomic stability and the packaging of sperm DNA. ..
  21. Liu W, Roemer S, Port A, Churchill M. CAF-1-induced oligomerization of histones H3/H4 and mutually exclusive interactions with Asf1 guide H3/H4 transitions among histone chaperones and DNA. Nucleic Acids Res. 2012;40:11229-39 pubmed publisher
    ..Thus, transition of H3/H4 from the Asf1-associated dimer to the DNA-associated tetramer is promoted by CAF-1-induced H3/H4 oligomerization. ..
  22. Kadyrova L, Dahal B, Kadyrov F. The Major Replicative Histone Chaperone CAF-1 Suppresses the Activity of the DNA Mismatch Repair System in the Cytotoxic Response to a DNA-methylating Agent. J Biol Chem. 2016;291:27298-27312 pubmed publisher
  23. Wyse B, Oshidari R, Rowlands H, Abbasi S, Yankulov K. RRM3 regulates epigenetic conversions in Saccharomyces cerevisiae in conjunction with Chromatin Assembly Factor I. Nucleus. 2016;7:405-14 pubmed publisher
    ..We propose that the stalling of DNA replication predisposes to epigenetic conversions and that RRM3 and CAF-I play key roles in this process. ..
  24. Glowczewski L, Waterborg J, Berman J. Yeast chromatin assembly complex 1 protein excludes nonacetylatable forms of histone H4 from chromatin and the nucleus. Mol Cell Biol. 2004;24:10180-92 pubmed
    ..In addition, our data support a model whereby Cac1p and Kap123 cooperate to ensure that only appropriately acetylated histone H4 proteins are imported into the nucleus. ..
  25. Burgess R, Zhou H, Han J, Li Q, Zhang Z. The SCFDia2 ubiquitin E3 ligase ubiquitylates Sir4 and functions in transcriptional silencing. PLoS Genet. 2012;8:e1002846 pubmed publisher
    ..These results demonstrate that the SCF(Dia2) complex is involved in transcriptional silencing, ubiquitylates Sir4, and regulates transcriptional silencing during the cell cycle. ..
  26. Bostelman L, Keller A, Albrecht A, Arat A, Thompson J. Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae. DNA Repair (Amst). 2007;6:383-95 pubmed
    ..The overall results indicate the existence of distinct and separable roles of histone H3 lysine-79 methylation in the response to UV damage, potentially serving to coordinate the various repair processes. ..
  27. Zunder R, Antczak A, Berger J, Rine J. Two surfaces on the histone chaperone Rtt106 mediate histone binding, replication, and silencing. Proc Natl Acad Sci U S A. 2012;109:E144-53 pubmed publisher
  28. Poon B, Mekhail K. Effects of Perinuclear Chromosome Tethers in the Telomeric URA3/5FOA System Reflect Changes to Gene Silencing and not Nucleotide Metabolism. Front Genet. 2012;3:144 pubmed publisher
    ..This is key to understanding relationships between telomere positioning, chromatin silencing, and lifespan. ..
  29. Johnston S, Enomoto S, Schneper L, McClellan M, Twu F, Montgomery N, et al. CAC3(MSI1) suppression of RAS2(G19V) is independent of chromatin assembly factor I and mediated by NPR1. Mol Cell Biol. 2001;21:1784-94 pubmed
    ..this mechanism and found that CAC3 suppression of RAS/cAMP signal transduction was independent of either CAC1 or CAC2, subunits required for CAF-I function...
  30. Yu Y, Srinivasan M, Nakanishi S, Leatherwood J, Shilatifard A, Sternglanz R. A conserved patch near the C terminus of histone H4 is required for genome stability in budding yeast. Mol Cell Biol. 2011;31:2311-25 pubmed publisher
  31. Haber J, Braberg H, Wu Q, Alexander R, Haase J, Ryan C, et al. Systematic triple-mutant analysis uncovers functional connectivity between pathways involved in chromosome regulation. Cell Rep. 2013;3:2168-78 pubmed publisher
    ..We have used this approach to interrogate partially redundant pairs of genes in S. cerevisiae, including ASF1 and CAC1, two histone chaperones...
  32. Sharp J, Rizki G, Kaufman P. Regulation of histone deposition proteins Asf1/Hir1 by multiple DNA damage checkpoint kinases in Saccharomyces cerevisiae. Genetics. 2005;171:885-99 pubmed
    ..display defects in telomeric gene silencing, silencing was dramatically reduced in cells lacking both Mec1 and the Cac1 subunit of CAF-1...
  33. Feser J, Truong D, Das C, Carson J, KIEFT J, Harkness T, et al. Elevated histone expression promotes life span extension. Mol Cell. 2010;39:724-35 pubmed publisher
    ..This study indicates that maintenance of the fundamental chromatin structure is critical for slowing down the aging process and reveals that increasing the histone supply extends life span. ..
  34. Sharp J, Krawitz D, Gardner K, Fox C, Kaufman P. The budding yeast silencing protein Sir1 is a functional component of centromeric chromatin. Genes Dev. 2003;17:2356-61 pubmed
    ..Sir1 bound to Cac1, a subunit of chromatin assembly factor I (CAF-I), and helped to retain Cac1 at centromeric loci...
  35. Sauer P, Timm J, Liu D, Sitbon D, Boeri Erba E, Velours C, et al. Insights into the molecular architecture and histone H3-H4 deposition mechanism of yeast Chromatin assembly factor 1. elife. 2017;6: pubmed publisher
    ..We identify a new DNA-binding domain in the large Cac1 subunit of CAF1, which is required for high-affinity DNA binding by the CAF1 three-subunit complex, and which is ..
  36. VanDemark A, Blanksma M, Ferris E, Heroux A, Hill C, Formosa T. The structure of the yFACT Pob3-M domain, its interaction with the DNA replication factor RPA, and a potential role in nucleosome deposition. Mol Cell. 2006;22:363-74 pubmed
    ..These results support the model that the FACT family has an essential role in constructing nucleosomes during DNA replication, and suggest that RPA contributes to this process. ..
  37. Burgess R, Han J, Zhang Z. The Ddc1-Mec3-Rad17 sliding clamp regulates histone-histone chaperone interactions and DNA replication-coupled nucleosome assembly in budding yeast. J Biol Chem. 2014;289:10518-29 pubmed publisher
    ..These results support the idea that the 9-1-1 checkpoint protein regulates DNA replication-coupled nucleosome assembly in part through regulating histone-histone chaperone interactions. ..
  38. Tsabar M, Waterman D, Aguilar F, Katsnelson L, Eapen V, Memisoglu G, et al. Asf1 facilitates dephosphorylation of Rad53 after DNA double-strand break repair. Genes Dev. 2016;30:1211-24 pubmed publisher
  39. Zhu X, Démolis N, Jacquet M, Michaeli T. MSI1 suppresses hyperactive RAS via the cAMP-dependent protein kinase and independently of chromatin assembly factor-1. Curr Genet. 2000;38:60-70 pubmed
    ..MSI1 appears to provide two distinct roles in chromatin modeling as a component of yCAF-1, and in the inhibition of RAS signaling by modulating PKA. ..
  40. Pratt Z, Drehman B, Miller M, Johnston S. Mutual interdependence of MSI1 (CAC3) and YAK1 in Saccharomyces cerevisiae. J Mol Biol. 2007;368:30-43 pubmed
    ..Taken together, these data demonstrate a novel interaction between Msi1p and Yak1p in which each protein influences the activity of the other. ..
  41. Janke R, King G, Kupiec M, Rine J. Pivotal roles of PCNA loading and unloading in heterochromatin function. Proc Natl Acad Sci U S A. 2018;115:E2030-E2039 pubmed publisher
    ..Collectively, these data identified a mechanism by which chromatin reassembly is coordinated with DNA replication to maintain silencing through S-phase. ..
  42. Liu Y, Huang H, Zhou B, Wang S, Hu Y, Li X, et al. Structural analysis of Rtt106p reveals a DNA binding role required for heterochromatin silencing. J Biol Chem. 2010;285:4251-62 pubmed publisher
    ..Our results uncover the structural basis of the diverse functions of Rtt106p and provide new insights into its cellular roles. ..
  43. Revers L, Cardone J, Bonatto D, Saffi J, Grey M, Feldmann H, et al. Thermoconditional modulation of the pleiotropic sensitivity phenotype by the Saccharomyces cerevisiae PRP19 mutant allele pso4-1. Nucleic Acids Res. 2002;30:4993-5003 pubmed
    ..Amongst 24 interacting clones isolated in a two-hybrid screening, seven could be identified as parts of the RAD2, RLF2 and DBR1 genes...
  44. Clemente Ruiz M, González Prieto R, Prado F. Histone H3K56 acetylation, CAF1, and Rtt106 coordinate nucleosome assembly and stability of advancing replication forks. PLoS Genet. 2011;7:e1002376 pubmed publisher
  45. Banerjee S, Myung K. Increased genome instability and telomere length in the elg1-deficient Saccharomyces cerevisiae mutant are regulated by S-phase checkpoints. Eukaryot Cell. 2004;3:1557-66 pubmed
  46. Sharp J, Franco A, Osley M, Kaufman P. Chromatin assembly factor I and Hir proteins contribute to building functional kinetochores in S. cerevisiae. Genes Dev. 2002;16:85-100 pubmed
    ..Finally, CAF-I subunits and Hir1 are enriched at centromeres, indicating that these proteins make a direct contribution to centromeric chromatin structures. ..
  47. Matsuda K, Makise M, Sueyasu Y, Takehara M, Asano T, Mizushima T. Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins. FEMS Yeast Res. 2007;7:1263-9 pubmed
    ..We discuss roles of these interactions in functions of ORC. ..
  48. Yang J, Zhang X, Feng J, Leng H, Li S, Xiao J, et al. The Histone Chaperone FACT Contributes to DNA Replication-Coupled Nucleosome Assembly. Cell Rep. 2016;14:1128-1141 pubmed publisher
    ..Therefore, FACT collaborates with CAF-1 and Rtt106 in RC nucleosome assembly. ..
  49. Saka K, Takahashi A, Sasaki M, Kobayashi T. More than 10% of yeast genes are related to genome stability and influence cellular senescence via rDNA maintenance. Nucleic Acids Res. 2016;44:4211-21 pubmed publisher
  50. Fennessy R, Owen Hughes T. Establishment of a promoter-based chromatin architecture on recently replicated DNA can accommodate variable inter-nucleosome spacing. Nucleic Acids Res. 2016;44:7189-203 pubmed publisher
    ..This indicates that the chromatin remodelling enzymes responsible for spacing nucleosomes are capable of organizing nucleosomes with a range of different linker DNA lengths. ..
  51. Schmidt K, Wu J, Kolodner R. Control of translocations between highly diverged genes by Sgs1, the Saccharomyces cerevisiae homolog of the Bloom's syndrome protein. Mol Cell Biol. 2006;26:5406-20 pubmed
    ..mutations in the genes encoding the checkpoint proteins Mec3, Rad24, Rad9, or Rfc5, the chromatin assembly factors Cac1 or Asf1, and the DNA helicase Rrm3...
  52. Liu W, Roemer S, Zhou Y, Shen Z, Dennehey B, Balsbaugh J, et al. The Cac1 subunit of histone chaperone CAF-1 organizes CAF-1-H3/H4 architecture and tetramerizes histones. elife. 2016;5: pubmed publisher
    ..reveal interactions that are essential for CAF-1 function in budding yeast, and importantly indicate that the Cac1 subunit functions as a scaffold within the CAF-1-H3/H4 complex...
  53. Lopes da Rosa J, Holik J, Green E, Rando O, Kaufman P. Overlapping regulation of CenH3 localization and histone H3 turnover by CAF-1 and HIR proteins in Saccharomyces cerevisiae. Genetics. 2011;187:9-19 pubmed publisher
    ..chromatin immunoprecipitation analyses demonstrated broader distribution of Cse4 outside of centromeres in cac1? hir1? double mutant cells that lack both CAF-1 and HIR complexes than in either single mutant...
  54. Poveda A, Sendra R. Site specificity of yeast histone acetyltransferase B complex in vivo. FEBS J. 2008;275:2122-36 pubmed publisher
    ..Finally, the exchange of Lys for Arg at position 12 of histone H4 did not interfere with histone H4 association with the complex, but prevented acetylation on Lys5 by the HAT-B enzyme, in vivo as well as in vitro. ..
  55. Iida T, Araki H. Noncompetitive counteractions of DNA polymerase epsilon and ISW2/yCHRAC for epigenetic inheritance of telomere position effect in Saccharomyces cerevisiae. Mol Cell Biol. 2004;24:217-27 pubmed
    ..We therefore propose that inheritance of specific epigenetic states of a telomere requires at least two counteracting regulators. ..