Gene Symbol: SLD2
Description: Sld2p
Alias: DRC1, Sld2p
Species: Saccharomyces cerevisiae S288c
Products:     SLD2

Top Publications

  1. 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
    ..In budding yeast (Saccharomyces cerevisiae), the replication protein Sld2 (ref...
  2. Masumoto H, Muramatsu S, Kamimura Y, Araki H. S-Cdk-dependent phosphorylation of Sld2 essential for chromosomal DNA replication in budding yeast. Nature. 2002;415:651-5 pubmed
    ..Here we show that Sld2 (ref. 4) (also known as Drc1; ref...
  3. Wang H, Elledge S. Genetic and physical interactions between DPB11 and DDC1 in the yeast DNA damage response pathway. Genetics. 2002;160:1295-304 pubmed
    ..These results suggest that DPB11 and DDC1 may function in the same or parallel pathways after DNA damage and that DDC1 may play a role in responding to replication defects. ..
  4. 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
    ..In this study, we characterized SLD2, encoding an essential 52-kDa protein...
  5. 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...
  6. Tak Y, Tanaka Y, Endo S, Kamimura Y, Araki H. A CDK-catalysed regulatory phosphorylation for formation of the DNA replication complex Sld2-Dpb11. EMBO J. 2006;25:1987-96 pubmed
    Phosphorylation often regulates protein-protein interactions to control biological reactions. The Sld2 and Dpb11 proteins of budding yeast form a phosphorylation-dependent complex that is essential for chromosomal DNA replication...
  7. 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
    ..Co-expression of this fusion with a phospho-mimicking mutant in a second essential CDK substrate, Sld2, promotes DNA replication in the absence of S-CDK...
  8. Wang H, Elledge S. DRC1, DNA replication and checkpoint protein 1, functions with DPB11 to control DNA replication and the S-phase checkpoint in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1999;96:3824-9 pubmed
    ..Here we describe a gene, DRC1, isolated as a dosage suppressor of dpb11-1...
  9. 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. ..

More Information


  1. 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 yeast, ..
  2. Kanter D, Kaplan D. Sld2 binds to origin single-stranded DNA and stimulates DNA annealing. Nucleic Acids Res. 2011;39:2580-92 pubmed publisher
    b>Sld2 is essential for the initiation of DNA replication, but the mechanism underlying its role in replication is not fully understood...
  3. Puddu F, Piergiovanni G, Plevani P, Muzi Falconi M. Sensing of replication stress and Mec1 activation act through two independent pathways involving the 9-1-1 complex and DNA polymerase ?. PLoS Genet. 2011;7:e1002022 pubmed publisher
  4. Tang X, Orlicky S, Liu Q, Willems A, Sicheri F, Tyers M. Genome-wide surveys for phosphorylation-dependent substrates of SCF ubiquitin ligases. Methods Enzymol. 2005;399:433-58 pubmed
    ..Both methods have identified novel substrates of Cdc4 and may, in principle, be used to identify numerous new substrates of other SCF and SCF-like complexes from yeast to humans. ..
  5. 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
    ..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...
  6. 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
    ..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...
  7. 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. ..
  8. Li J, Tetzlaff M, Elledge S. Identification of MSA1, a cell cycle-regulated, dosage suppressor of drc1/sld2 and dpb11 mutants. Cell Cycle. 2008;7:3388-98 pubmed
    The Dpb11 and Drc1/Sld2 proteins form a complex that is critical for the initiation of DNA replication. In this study we identify MSA1 as a high copy suppressor of a drc1-1 mutant...
  9. 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. ..
  10. Bloom J, Cross F. Novel role for Cdc14 sequestration: Cdc14 dephosphorylates factors that promote DNA replication. Mol Cell Biol. 2007;27:842-53 pubmed not sequestered, it efficiently dephosphorylates a subset of Cdk1 substrates including the replication factors, Sld2 and Dpb2...
  11. 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
    The Cdc45-Mcm2-7-GINS (CMG) complex is the replication fork helicase in eukaryotes. Synthetic lethal with Dpb11-1 (Sld2) is required for the initiation of DNA replication, and the S phase cyclin-dependent kinase (S-CDK) phosphorylates ..
  12. Dhingra N, Bruck I, Smith S, Ning B, Kaplan D. Dpb11 protein helps control assembly of the Cdc45·Mcm2-7·GINS replication fork helicase. J Biol Chem. 2015;290:7586-601 pubmed publisher
    ..Dpb11 binds to S-phase cyclin-dependent kinase-phosphorylated Sld2 and Sld3 to form a ternary complex during S phase...
  13. Navadgi Patil V, Kumar S, Burgers P. The unstructured C-terminal tail of yeast Dpb11 (human TopBP1) protein is dispensable for DNA replication and the S phase checkpoint but required for the G2/M checkpoint. J Biol Chem. 2011;286:40999-1007 pubmed publisher
    ..Together with aromatic motifs identified previously in the Ddc1 subunit of 9-1-1, another activator of Mec1 kinase, they define a consensus structure for Mec1 activation. ..
  14. Tanaka S, Araki H. Multiple regulatory mechanisms to inhibit untimely initiation of DNA replication are important for stable genome maintenance. PLoS Genet. 2011;7:e1002136 pubmed publisher
    ..Our data indicate that cells preserve a low level of the initiation factor Sld2 to prevent untimely initiation during the normal cell cycle in addition to controlling the phosphorylation of Sld2 ..
  15. Bruck I, Kaplan D. The replication initiation protein Sld2 regulates helicase assembly. J Biol Chem. 2014;289:1948-59 pubmed publisher
    ..b>Sld2 is required for the initiation of DNA replication in budding yeast...
  16. Reusswig K, Zimmermann F, Galanti L, Pfander B. Robust Replication Control Is Generated by Temporal Gaps between Licensing and Firing Phases and Depends on Degradation of Firing Factor Sld2. Cell Rep. 2016;17:556-569 pubmed publisher
    ..We find that gap size critically depends on phosphorylation-dependent degradation of the firing factor Sld2 mediated by CDK, DDK, Mck1, and Cdc5 kinases and the ubiquitin-ligases Dma1/2...