Gene Symbol: SLD3
Description: Sld3p
Alias: Sld3p
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Zegerman P, Diffley J. Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast. Nature. 2007;445:281-5 pubmed
    ..We identified two S phase CDK (S-CDK) phosphorylation sites in the budding yeast Sld3 protein that, together, are essential for DNA replication...
  2. Kamimura Y, Tak Y, Sugino A, Araki H. Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA replication in Saccharomyces cerevisiae. EMBO J. 2001;20:2097-107 pubmed
    ..Here we show that throughout the cell cycle in Saccharomyces cerevisiae, Cdc45 forms a complex with a novel factor, Sld3. Consistently, Sld3 and Cdc45 associate simultaneously with replication origins in the chromatin ..
  3. Tanaka T, Umemori T, Endo S, Muramatsu S, Kanemaki M, Kamimura Y, et al. Sld7, an Sld3-associated protein required for efficient chromosomal DNA replication in budding yeast. EMBO J. 2011;30:2019-30 pubmed publisher
    ..Throughout the cell cycle, Sld7 forms a complex with Sld3, which associates with replication origins in a complex with Cdc45, binds to Dpb11 when phosphorylated by cyclin-..
  4. Lopez Mosqueda J, Maas N, Jonsson Z, Defazio Eli L, Wohlschlegel J, Toczyski D. Damage-induced phosphorylation of Sld3 is important to block late origin firing. Nature. 2010;467:479-83 pubmed publisher
    ..Here we show that the replication initiation protein Sld3 is phosphorylated by Rad53, and that this phosphorylation, along with phosphorylation of the Cdc7 kinase regulatory ..
  5. Tanaka S, Nakato R, Katou Y, Shirahige K, Araki H. Origin association of Sld3, Sld7, and Cdc45 proteins is a key step for determination of origin-firing timing. Curr Biol. 2011;21:2055-63 pubmed publisher
    ..We show that origin association of the low-abundance replication proteins Sld3, Sld7, and Cdc45 is the key to determining the temporal order of origin firing...
  6. Tanaka S, Umemori T, Hirai K, Muramatsu S, Kamimura Y, Araki H. CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast. Nature. 2007;445:328-32 pubmed
    ..Although Cdc45 is not an essential CDK substrate, CDK-dependent phosphorylation of Sld3, which associates with Cdc45 (ref. 5), is essential and generates a binding site for Dpb11...
  7. 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;30:4805-14 pubmed publisher
    ..Here, we show that the two CDK substrates Sld3 and Sld2 and their binding partner Dpb11, together with the DDK subunit Dbf4 are in low abundance in the budding ..
  8. Zegerman P, Diffley J. Checkpoint-dependent inhibition of DNA replication initiation by Sld3 and Dbf4 phosphorylation. Nature. 2010;467:474-8 pubmed publisher
    ..CDK phosphorylation of two key initiation factors, Sld2 and Sld3, promotes essential interactions with Dpb11 (refs 2-4), whereas DDK acts by phosphorylating subunits of the Mcm2-7 ..
  9. Kanemaki M, Labib K. Distinct roles for Sld3 and GINS during establishment and progression of eukaryotic DNA replication forks. EMBO J. 2006;25:1753-63 pubmed
    ..of Cdc45 at nascent forks is a highly regulated and poorly understood process that requires, in budding yeast, the Sld3 protein and the GINS complex...

More Information


  1. Simoneau A, Ricard Ã, Weber S, Hammond Martel I, Wong L, Sellam A, et al. Chromosome-wide histone deacetylation by sirtuins prevents hyperactivation of DNA damage-induced signaling upon replicative stress. Nucleic Acids Res. 2016;44:2706-26 pubmed publisher
    ..Overall, our data support the concept that chromosome-wide histone deacetylation by sirtuins is critical to mitigate growth defects caused by endogenous genotoxins. ..
  2. Lydeard J, Lipkin Moore Z, Sheu Y, Stillman B, Burgers P, Haber J. Break-induced replication requires all essential DNA replication factors except those specific for pre-RC assembly. Genes Dev. 2010;24:1133-44 pubmed publisher
    ..These results suggest that origin-independent BIR involves cross-talk between normal DNA replication factors and PRR. ..
  3. Bruck I, Kaplan D. GINS and Sld3 compete with one another for Mcm2-7 and Cdc45 binding. J Biol Chem. 2011;286:14157-67 pubmed publisher
    b>Sld3 is essential for the initiation of DNA replication, but Sld3 does not travel with a replication fork. GINS binds to Cdc45 and Mcm2-7 to form the replication fork helicase in eukaryotes...
  4. Deegan T, Yeeles J, Diffley J. Phosphopeptide binding by Sld3 links Dbf4-dependent kinase to MCM replicative helicase activation. EMBO J. 2016;35:961-73 pubmed publisher
    ..Here we show that Sld3, previously shown to be an essential CDK and Rad53 substrate, is recruited to the inactive MCM double hexamer in a ..
  5. Yoshida K, Bacal J, Desmarais D, Padioleau I, Tsaponina O, Chabes A, et al. The histone deacetylases sir2 and rpd3 act on ribosomal DNA to control the replication program in budding yeast. Mol Cell. 2014;54:691-7 pubmed publisher
    ..Together, these data indicate that HDACs control the replication timing program in budding yeast by modulating the ability of repeated origins to compete with single-copy origins for limiting initiation factors. ..
  6. Herrera M, Tognetti S, Riera A, Zech J, Clarke P, Fernández Cid A, et al. A reconstituted system reveals how activating and inhibitory interactions control DDK dependent assembly of the eukaryotic replicative helicase. Nucleic Acids Res. 2015;43:10238-50 pubmed publisher
    ..advanced reconstituted-system to study helicase activation in-solution and discovered that individual factors like Sld3 and Sld2 can bind directly to the pre-RC, while Cdc45 cannot...
  7. Bruck I, Kaplan D. Origin single-stranded DNA releases Sld3 protein from the Mcm2-7 complex, allowing the GINS tetramer to bind the Mcm2-7 complex. J Biol Chem. 2011;286:18602-13 pubmed publisher
    ..In budding yeast, Sld3, Sld2, and Dpb11 are required for the initiation of DNA replication, but Sld3 and Dpb11 do not travel with the ..
  8. Natsume T, Müller C, Katou Y, Retkute R, Gierlinski M, Araki H, et al. Kinetochores coordinate pericentromeric cohesion and early DNA replication by Cdc7-Dbf4 kinase recruitment. Mol Cell. 2013;50:661-74 pubmed publisher
    ..This promptly recruits Sld3-Sld7 replication initiator proteins to pericentromeric replication origins so that they initiate replication early ..
  9. Bruck I, Dhingra N, Martinez M, Kaplan D. Dpb11 may function with RPA and DNA to initiate DNA replication. PLoS ONE. 2017;12:e0177147 pubmed publisher
    ..We also propose an alternative model, wherein Dpb11-DNA interaction is required for some other function in DNA replication initiation, such as helicase activation. ..
  10. Tanaka S, Komeda Y, Umemori T, Kubota Y, Takisawa H, Araki H. Efficient initiation of DNA replication in eukaryotes requires Dpb11/TopBP1-GINS interaction. Mol Cell Biol. 2013;33:2614-22 pubmed publisher
    ..pair (BRCT1 and -2) and the C-terminal pair (BRCT3 and -4) bind to cyclin-dependent kinase (CDK)-phosphorylated Sld3 and Sld2, respectively. These phosphorylation-dependent interactions trigger the initiation of DNA replication...
  11. Sheu Y, Kinney J, Stillman B. Concerted activities of Mcm4, Sld3, and Dbf4 in control of origin activation and DNA replication fork progression. Genome Res. 2016;26:315-30 pubmed publisher
    ..Following replication stress in S phase, Dbf4 and Sld3, an initiation factor and essential target of Cyclin-Dependent Kinase (CDK), are targets of the checkpoint kinase ..
  12. Takayama Y, Kamimura Y, Okawa M, Muramatsu S, Sugino A, Araki H. GINS, a novel multiprotein complex required for chromosomal DNA replication in budding yeast. Genes Dev. 2003;17:1153-65 pubmed
    ..In budding yeast, assembly of Dpb11 and the Sld3-Cdc45 complex on the pre-RC at origins is required for loading DNA polymerases...
  13. Bruck I, Kanter D, Kaplan D. Enabling association of the GINS protein tetramer with the mini chromosome maintenance (Mcm)2-7 protein complex by phosphorylated Sld2 protein and single-stranded origin DNA. J Biol Chem. 2011;286:36414-26 pubmed publisher
    ..Furthermore, origin ssDNA may stimulate the formation of the CMG complex by alleviating inhibitory interactions between Sld2 with Mcm2-7. ..
  14. Bruck I, Kaplan D. Conserved mechanism for coordinating replication fork helicase assembly with phosphorylation of the helicase. Proc Natl Acad Sci U S A. 2015;112:11223-8 pubmed publisher
    Dbf4-dependent kinase (DDK) phosphorylates minichromosome maintenance 2 (Mcm2) during S phase in yeast, and Sld3 recruits cell division cycle 45 (Cdc45) to minichromosome maintenance 2-7 (Mcm2-7)...
  15. Ma L, Zhai Y, Feng D, Chan T, Lu Y, Fu X, et al. Identification of novel factors involved in or regulating initiation of DNA replication by a genome-wide phenotypic screen in Saccharomyces cerevisiae. Cell Cycle. 2010;9:4399-410 pubmed
    ..These data suggest that Ctf1p and Ctf18p together play important roles in regulating the initiation of DNA replication. ..
  16. Itou H, Shirakihara Y, Araki H. The quaternary structure of the eukaryotic DNA replication proteins Sld7 and Sld3. Acta Crystallogr D Biol Crystallogr. 2015;71:1649-56 pubmed publisher
    ..Yeast Sld3 and its metazoan counterpart treslin are the hub proteins mediating protein associations critical for formation of ..
  17. Bruck I, Kaplan D. Cdc45 protein-single-stranded DNA interaction is important for stalling the helicase during replication stress. J Biol Chem. 2013;288:7550-63 pubmed publisher
    ..These data suggest that Cdc45-ssDNA interaction is important for stalling the helicase during replication stress. ..
  18. Mattarocci S, Shyian M, Lemmens L, Damay P, Altintas D, Shi T, et al. Rif1 controls DNA replication timing in yeast through the PP1 phosphatase Glc7. Cell Rep. 2014;7:62-9 pubmed publisher
    ..with Rif1 in an RVxF/SILK-dependent manner and that two proteins implicated in pre-RC activation, Mcm4 and Sld3, display increased Dbf4-dependent kinase (DDK) phosphorylation in rif1 mutants...
  19. Duch A, Palou G, Jonsson Z, Palou R, Calvo E, Wohlschlegel J, et al. A Dbf4 mutant contributes to bypassing the Rad53-mediated block of origins of replication in response to genotoxic stress. J Biol Chem. 2011;286:2486-91 pubmed publisher
    ..We show here that dbf4(7A) is a bona fide intra-S phase checkpoint bypass allele that contributes to abrogating the Rad53 block of origin firing in response to genotoxic stress. ..
  20. Ohya T, Kawasaki Y, Hiraga S, Kanbara S, Nakajo K, Nakashima N, et al. The DNA polymerase domain of pol(epsilon) is required for rapid, efficient, and highly accurate chromosomal DNA replication, telomere length maintenance, and normal cell senescence in Saccharomyces cerevisiae. J Biol Chem. 2002;277:28099-108 pubmed
    ..These results indicate that the DNA polymerase domain of Pol2p is required for rapid, efficient, and highly accurate chromosomal DNA replication in yeast. ..
  21. Najor N, Weatherford L, Brush G. Prevention of DNA Rereplication Through a Meiotic Recombination Checkpoint Response. G3 (Bethesda). 2016;6:3869-3881 pubmed publisher
    ..S phase checkpoint response are also involved, based on the behavior of cells containing mutations in the DBF4 and SLD3 DNA replication genes...
  22. Itou H, Muramatsu S, Shirakihara Y, Araki H. Crystal structure of the homology domain of the eukaryotic DNA replication proteins Sld3/Treslin. Structure. 2014;22:1341-1347 pubmed publisher
    ..Yeast Sld3 and its metazoan counterpart Treslin are the hub proteins mediating protein associations critical for the helicase ..
  23. Wang G, Tong X, Weng S, Zhou H. Multiple phosphorylation of Rad9 by CDK is required for DNA damage checkpoint activation. Cell Cycle. 2012;11:3792-800 pubmed publisher
    ..We propose that multiple phosphorylation of Rad9 by CDK may provide a more robust system to allow Rad9 to control cell cycle-dependent DNA damage checkpoint activation. ..
  24. Muramatsu S, Hirai K, Tak Y, Kamimura Y, Araki H. CDK-dependent complex formation between replication proteins Dpb11, Sld2, Pol (epsilon}, and GINS in budding yeast. Genes Dev. 2010;24:602-12 pubmed publisher
    ..CDK phosphorylates two yeast replication proteins, Sld3 and Sld2, both of which bind to Dpb11 when phosphorylated...
  25. Kamimura Y, Masumoto H, Sugino A, Araki H. Sld2, which interacts with Dpb11 in Saccharomyces cerevisiae, is required for chromosomal DNA replication. Mol Cell Biol. 1998;18:6102-9 pubmed
    ..These results strongly suggest the involvement of the Dpb11-Sld2 complex in a step close to the initiation of DNA replication. ..