Gene Symbol: DPB11
Description: protein kinase activating protein DPB11
Alias: protein kinase activating protein DPB11
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Puddu F, Granata M, di Nola L, Balestrini A, Piergiovanni G, Lazzaro F, et al. Phosphorylation of the budding yeast 9-1-1 complex is required for Dpb11 function in the full activation of the UV-induced DNA damage checkpoint. Mol Cell Biol. 2008;28:4782-93 pubmed publisher
    ..We found that the replication factor Dpb11 is the keystone of this second pathway...
  2. Granata M, Lazzaro F, Novarina D, Panigada D, Puddu F, Abreu C, et al. Dynamics of Rad9 chromatin binding and checkpoint function are mediated by its dimerization and are cell cycle-regulated by CDK1 activity. PLoS Genet. 2010;6: pubmed publisher
    ..CDK1-dependent phosphorylation of Rad9 on Ser11 leads to specific interaction with Dpb11, allowing Rad53 activation and bypassing the requirement for the histone branch.
  3. Edwards S, Li C, Levy D, Brown J, Snow P, Campbell J. Saccharomyces cerevisiae DNA polymerase epsilon and polymerase sigma interact physically and functionally, suggesting a role for polymerase epsilon in sister chromatid cohesion. Mol Cell Biol. 2003;23:2733-48 pubmed
    ..We also show that trf5 Delta mutants, like trf4 Delta mutants, are defective in DNA repair and sister chromatid cohesion. ..
  4. 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...
  5. Ohya T, Maki S, Kawasaki Y, Sugino A. Structure and function of the fourth subunit (Dpb4p) of DNA polymerase epsilon in Saccharomyces cerevisiae. Nucleic Acids Res. 2000;28:3846-52 pubmed
    ..A double mutant haploid strain carrying the Deltadpb4 deletion and either pol2-11 or dpb11-1 is lethal at all temperatures tested...
  6. 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
    The DPB11 gene, which genetically interacts with DNA polymerase II (epsilon), one of three replicative DNA polymerases, is required for DNA replication and the S phase checkpoint in Saccharomyces cerevisiae...
  7. Germann S, Oestergaard V, Haas C, Salis P, Motegi A, Lisby M. Dpb11/TopBP1 plays distinct roles in DNA replication, checkpoint response and homologous recombination. DNA Repair (Amst). 2011;10:210-24 pubmed publisher
    b>DPB11/TopBP1 is an essential evolutionarily conserved gene involved in initiation of DNA replication and checkpoint signaling...
  8. Mordes D, Nam E, Cortez D. Dpb11 activates the Mec1-Ddc2 complex. Proc Natl Acad Sci U S A. 2008;105:18730-4 pubmed publisher
    ..The S. cerevisiae BRCT repeat protein Dpb11 functions in the initiation of both DNA replication and cell cycle checkpoints...
  9. Navadgi Patil V, Burgers P. A tale of two tails: activation of DNA damage checkpoint kinase Mec1/ATR by the 9-1-1 clamp and by Dpb11/TopBP1. DNA Repair (Amst). 2009;8:996-1003 pubmed publisher
    ..A second, conserved activity of 9-1-1 is that of TopBP1/Cut5/Dpb11 recruitment to stalled replication sites; subsequent activation of Mec1/ATR is carried out by TopBP1/Cut5/Dpb11...

More Information


  1. Masumoto H, Sugino A, Araki H. Dpb11 controls the association between DNA polymerases alpha and epsilon and the autonomously replicating sequence region of budding yeast. Mol Cell Biol. 2000;20:2809-17 pubmed
    b>Dpb11 is required for chromosomal DNA replication and the S-phase checkpoint in Saccharomyces cerevisiae. Here, we report detection of a physical complex containing Dpb11 and DNA polymerase epsilon (Dpb11-Polepsilon complex)...
  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
    ..Moreover, the complex that contains, at least, Sld2 and Dpb11 (ref...
  3. 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
    ..Here we show that both an allele of CDC45 (JET1) and high-copy DPB11, in combination with Sld2-11D, separately confer CDK-independent DNA replication...
  4. 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
    ..action of a series of proteins, including regulators Cdc28/Clb and Dbf4/Cdc7 kinases, Orcs, Mcms, Cdc6, Cdc45, and Dpb11. Of these, Dpb11, an essential BRCT repeat protein, has remained particularly enigmatic...
  5. Araki H, Leem S, Phongdara A, Sugino A. Dpb11, which interacts with DNA polymerase II(epsilon) in Saccharomyces cerevisiae, has a dual role in S-phase progression and at a cell cycle checkpoint. Proc Natl Acad Sci U S A. 1995;92:11791-5 pubmed
    b>DPB11, a gene that suppresses mutations in two essential subunits of Saccharomyces cerevisiae DNA polymerase II(epsilon) encoded by POL2 and DPB2, was isolated on a multicopy plasmid...
  6. 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...
  7. 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
    Budding yeast Dpb11 (human TopBP1, fission yeast Cut5) is an essential protein required for replisome assembly and for the DNA damage checkpoint...
  8. Ohouo P, Bastos de Oliveira F, Almeida B, Smolka M. DNA damage signaling recruits the Rtt107-Slx4 scaffolds via Dpb11 to mediate replication stress response. Mol Cell. 2010;39:300-6 pubmed publisher
    ..Here, we found that Mec1 mediates a key interaction between the fork protein Dpb11 and the DNA repair scaffolds Slx4-Rtt107 to regulate replication stress response...
  9. Pfander B, Diffley J. Dpb11 coordinates Mec1 kinase activation with cell cycle-regulated Rad9 recruitment. EMBO J. 2011;30:4897-907 pubmed publisher
    ..One such mediator is the Saccharomyces cerevisiae Dpb11 protein, which binds to and activates the apical checkpoint kinase, Mec1...
  10. Navadgi Patil V, Burgers P. Yeast DNA replication protein Dpb11 activates the Mec1/ATR checkpoint kinase. J Biol Chem. 2008;283:35853-9 pubmed publisher
    ..b>Dpb11 (Schizosaccharomyces pombe Cut5/Rad4 or human TopBP1) is an essential protein required for the initiation of DNA ..
  11. 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
    b>DPB11 is essential for DNA replication and S/M checkpoint control in Saccharomyces cerevisiae. The Dpb11 protein contains four BRCT domains, which have been proposed to be involved in protein-protein interactions...
  12. 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
    ..kinase Mec1 is required to activate both signaling cascades together with the 9-1-1 PCNA-like complex and the Dpb11 (hTopBP1) protein. After DNA damage, Dpb11 is also needed to recruit the adaptor protein Rad9 (h53BP1)...
  13. 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...
  14. Balint A, Kim T, Gallo D, Cussiol J, Bastos de Oliveira F, Yimit A, et al. Assembly of Slx4 signaling complexes behind DNA replication forks. EMBO J. 2015;34:2182-97 pubmed publisher
    ..Slx4 is essential for recruiting the Mec1 activator Dpb11 behind stressed replication forks, and Slx4 complexes are important for full activity of Mec1...
  15. Gritenaite D, Princz L, Szakal B, Bantele S, Wendeler L, Schilbach S, et al. A cell cycle-regulated Slx4-Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication. Genes Dev. 2014;28:1604-19 pubmed publisher
    ..Central to this regulation is a conserved complex comprising the scaffold proteins Dpb11 and Slx4 that is under stringent control...
  16. 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. ..
  17. Burgers P. Eukaryotic DNA polymerases in DNA replication and DNA repair. Chromosoma. 1998;107:218-27 pubmed
    ..The role of DNA polymerase beta in base-excision repair is well established for mammalian systems, but in yeast, DNA polymerase delta appears to fulfill that function. ..
  18. Germann S, Schramke V, Pedersen R, Gallina I, Eckert Boulet N, Oestergaard V, et al. TopBP1/Dpb11 binds DNA anaphase bridges to prevent genome instability. J Cell Biol. 2014;204:45-59 pubmed publisher
    ..cerevisiae and the avian DT40 cell line as model systems for studying DNA anaphase bridges and show that TopBP1/Dpb11 plays an evolutionarily conserved role in their metabolism...
  19. 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
    b>Dpb11 is required for the initiation of DNA replication in budding yeast. Dpb11 binds to S-phase cyclin-dependent kinase-phosphorylated Sld2 and Sld3 to form a ternary complex during S phase...
  20. 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
    ..These data indicate that the intra-S-phase checkpoint functions to block late origin firing in adverse conditions to prevent genomic instability and maximize cell survival. ..
  21. 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
    b>Dpb11 is required for the initiation of DNA replication in budding yeast...
  22. 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
    ..These data suggest a conserved mechanism for replication initiation: Sld3/Treslin coordinates Cdc45 recruitment to Mcm2-7 with DDK phosphorylation of Mcm2 during S phase. ..
  23. Princz L, Gritenaite D, Pfander B. The Slx4-Dpb11 scaffold complex: coordinating the response to replication fork stalling in S-phase and the subsequent mitosis. Cell Cycle. 2015;14:488-94 pubmed publisher
    ..In budding yeast, specifically during mitosis, Slx4 and Dpb11 form a cell cycle kinase-dependent complex with the Mus81-Mms4 structure-selective endonuclease, which allows ..
  24. Tanaka S, Diffley J. Interdependent nuclear accumulation of budding yeast Cdt1 and Mcm2-7 during G1 phase. Nat Cell Biol. 2002;4:198-207 pubmed
    ..Cdt1p interacts with the Mcm2--7p complex, and the nuclear accumulation of these proteins during G1 is interdependent. This coregulation of Cdt1p and Mcm2-7p represents a novel level of pre-RC control. ..
  25. 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. ..
  26. 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
    ..Although Dpb11 interacts with CDK-phosphorylated Rad9, we provide evidence showing that elimination of this interaction does not ..
  27. Navadgi Patil V, Burgers P. Cell-cycle-specific activators of the Mec1/ATR checkpoint kinase. Biochem Soc Trans. 2011;39:600-5 pubmed publisher
    ..cerevisiae; Ddc1-Mec3-Rad17) and the DNA replication initiation factor Dpb11 (human TopBP1) are the two known activators of Mec1...
  28. 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 replication fork...
  29. Kapoor P, Bao Y, Xiao J, Luo J, Shen J, Persinger J, et al. Regulation of Mec1 kinase activity by the SWI/SNF chromatin remodeling complex. Genes Dev. 2015;29:591-602 pubmed publisher
    ..In vitro, SWI/SNF can activate Mec1 kinase activity in the absence of chromatin or known activators such as Dpb11. The subunit requirement of SWI/SNF-mediated Mec1 regulation differs from that of SWI/SNF-mediated chromatin ..
  30. 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
    b>Dpb11/Cut5/TopBP1 is evolutionarily conserved and is essential for the initiation of DNA replication in eukaryotes. The Dpb11 of the budding yeast Saccharomyces cerevisiae has four BRCT domains (BRCT1 to -4)...
  31. 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. ..
  32. Kawasaki Y, Hiraga S, Sugino A. Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae. Genes Cells. 2000;5:975-89 pubmed
  33. Myung K, Kolodner R. Suppression of genome instability by redundant S-phase checkpoint pathways in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2002;99:4500-7 pubmed
    ..These data support the view that spontaneous genome rearrangements result from DNA replication errors and indicate that there is a high degree of redundancy among the checkpoints that act in S phase to suppress such genome instability. ..
  34. Cussiol J, Jablonowski C, Yimit A, Brown G, Smolka M. Dampening DNA damage checkpoint signalling via coordinated BRCT domain interactions. EMBO J. 2015;34:1704-17 pubmed publisher
    ..MBD mimics the damage-induced Dpb11-Slx4-Rtt107 complex by synergistically interacting with lesion-specific phospho-sites in Ddc1 and H2A...
  35. Kanter D, Kaplan D. Sld2 binds to origin single-stranded DNA and stimulates DNA annealing. Nucleic Acids Res. 2011;39:2580-92 pubmed publisher
    ..The S-phase cyclin dependent kinase (S-CDK) triggers the association of Sld2 with Dpb11, and a phosphomimetic mutation of Sld2, Sld2T84D, functionally mimics the S-CDK phosphorylated state of Sld2...
  36. Bandhu A, Kang J, Fukunaga K, Goto G, Sugimoto K. Ddc2 mediates Mec1 activation through a Ddc1- or Dpb11-independent mechanism. PLoS Genet. 2014;10:e1004136 pubmed publisher
    ..Previous studies have established the model in which Ddc1, a subunit of the checkpoint clamp, and Dpb11, related to TopBP1, activate Mec1 directly and control DNA damage checkpoint responses at G1 and G2/M...
  37. Reid R, Fiorani P, Sugawara M, Bjornsti M. CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damage. Proc Natl Acad Sci U S A. 1999;96:11440-5 pubmed
    ..Two mutants isolated, cdc45-10 and dpb11-10, exhibited specific defects in DNA replication and a synthetic lethal phenotype in the absence of DNA damaging ..
  38. Princz L, Wild P, Bittmann J, Aguado F, Blanco M, Matos J, et al. Dbf4-dependent kinase and the Rtt107 scaffold promote Mus81-Mms4 resolvase activation during mitosis. EMBO J. 2017;36:664-678 pubmed publisher
    ..Therefore, Mus81 activation in mitosis involves at least three cell cycle kinases, CDK, Cdc5 and DDK Furthermore, tethering of the kinases in a stable complex with Mus81 is critical for efficient JM resolution. ..
  39. Ohouo P, Bastos de Oliveira F, Liu Y, Ma C, Smolka M. DNA-repair scaffolds dampen checkpoint signalling by counteracting the adaptor Rad9. Nature. 2013;493:120-4 pubmed publisher
    ..An Slx4-Rtt107 complex counteracts the checkpoint adaptor Rad9 by physically interacting with Dpb11 and phosphorylated histone H2A, two positive regulators of Rad9-dependent Rad53 activation...
  40. Bruck I, Kaplan D. The replication initiation protein Sld2 regulates helicase assembly. J Biol Chem. 2014;289:1948-59 pubmed publisher
    ..We also study a mutant of Sld2 that is defective in binding DNA, sld2-DNA, and find that sld2-DNA cells exhibit no GINS-Mcm2-7 interaction. These data suggest that Sld2 association with DNA is required for CMG assembly in S phase...
  41. 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. ..
  42. 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...
  43. Nunez L, Jesch S, Gaspar M, Almaguer C, Villa Garcia M, Ruiz Noriega M, et al. Cell wall integrity MAPK pathway is essential for lipid homeostasis. J Biol Chem. 2008;283:34204-17 pubmed publisher
    ..These results indicate that an intact cell wall integrity pathway is required for maintaining proper lipid homeostasis in yeast, especially when cells are grown in the absence of inositol. ..
  44. Ogiwara H, Ui A, Onoda F, Tada S, Enomoto T, Seki M. Dpb11, the budding yeast homolog of TopBP1, functions with the checkpoint clamp in recombination repair. Nucleic Acids Res. 2006;34:3389-98 pubmed
    b>Dpb11 is required for the loading of DNA polymerases alpha and epsilon on to DNA in chromosomal DNA replication and interacts with the DNA damage checkpoint protein Ddc1 in Saccharomyces cerevisiae...
  45. 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
    Genetic screening of yeast for sld (synthetic lethality with dpb11) mutations has identified replication proteins, including Sld2, -3, and -5, and clarified the molecular mechanisms underlying eukaryotic chromosomal DNA replication...
  46. 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 helicase...
  47. 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
    ..length caused by the elg1Delta mutation was suppressed by a defect in the DNA replication checkpoint, which suggests that DNA replication surveillance by Dpb11-Mec1/Tel1-Dun1 also has an important role in telomere length regulation.
  48. 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
    ..Our data thus link Rif1 to negative regulation of replication origin firing through recruitment of the Glc7 phosphatase. ..
  49. Kolodner R, Marsischky G. Eukaryotic DNA mismatch repair. Curr Opin Genet Dev. 1999;9:89-96 pubmed
    ..MMR proteins function in these processes in conjunction with components of nucleotide excision repair (NER) and, possibly, recombination. ..
  50. 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, Saccharomyces cerevisiae...
  51. Bantele S, Ferreira P, Gritenaite D, Boos D, Pfander B. Targeting of the Fun30 nucleosome remodeller by the Dpb11 scaffold facilitates cell cycle-regulated DNA end resection. elife. 2017;6: pubmed publisher
    ..yeast Fun30 and human SMARCAD1 are cell cycle-regulated by interaction with the DSB-localized scaffold protein Dpb11/TOPBP1, respectively...