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Gene Review:

DPB11 - Dpb11p

Saccharomyces cerevisiae S288c

Synonyms: DNA replication regulator DPB11, J0918, YJL090C

Wang, H. et al., Tak, Y.S. et al., Araki, H. et al., Tanaka, S. et al., Kamimura, Y. et al., et al.

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High impact information on DPB11

Because this complex is suggested to be essential for chromosomal DNA replication, it seems likely that S-Cdk positively regulates formation of the Sld2-Dpb11 complex and, consequently, chromosomal DNA replication [1].
Therefore, Dpb11, Sld3, Cdc45, and GINS assemble in a mutually dependent manner on replication origins to initiate DNA synthesis [2].
Without GINS, neither Dpb11 nor Cdc45 associates properly with chromatin DNA [2].
A CDK-catalysed regulatory phosphorylation for formation of the DNA replication complex Sld2-Dpb11 [3].
Dpb11 is the second BRCT-repeat protein shown to control Rad53 function, possibly indicating a general function for this class of proteins [4].

Biological context of DPB11

DRC1, DNA replication and checkpoint protein 1, functions with DPB11 to control DNA replication and the S-phase checkpoint in Saccharomyces cerevisiae [4].
The nucleotide sequence of the DPB11 gene revealed an open reading frame predicting an 87-kDa protein [5].
Disruption of DPB11 is lethal, indicating that DPB11 is essential for cell proliferation [5].
Genetic and physical interactions between DPB11 and DDC1 in the yeast DNA damage response pathway [6].
The Drc1 and Dpb11 proteins physically associate and function together to coordinate DNA replication and the cell cycle [4].

Associations of DPB11 with chemical compounds

Moreover, dpb11 cells are sensitive to hydroxyurea, methyl methanesulfonate, and UV irradiation [5].
Simultaneous alanine substitution for serine or threonine in all the canonical CDK-phosphorylation motifs severely reduces complex formation between Sld2 and Dpb11, and inhibits DNA replication [3].
Ddc1 as well as Dpb11 were required for homologous recombination induced by MMS [7].

Physical interactions of DPB11

Immunoprecipitation experiments confirmed that Dpb11 physically interacts with Sld2. sld2-6 cells were defective in DNA replication at the restrictive temperature, as were dpb11-1 cells [8].

Regulatory relationships of DPB11

We demonstrate that Dpb11 directly activates the Mec1 kinase in phosphorylating the downstream effector kinase Rad53 (human Chk1/2) and DNA bound RPA [9].

Other interactions of DPB11

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 [10].
The Schizosaccharomyces pombe homolog of DPB11, cut5, has been implicated in the DNA replication checkpoint as has the POL2 gene with which DPB11 genetically interacts [4].
DDC1 and DPB11 also interact genetically [6].
Both the JET1 mutation and high-copy DPB11 by-pass the requirement for Sld3 phosphorylation in DNA replication [10].
CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damage [11].

Analytical, diagnostic and therapeutic context of DPB11

The interaction between Sld2 and Dpb11 was detected in a two-hybrid assay [8].

References

S-Cdk-dependent phosphorylation of Sld2 essential for chromosomal DNA replication in budding yeast. Masumoto, H., Muramatsu, S., Kamimura, Y., Araki, H. Nature (2002) [Pubmed]
GINS, a novel multiprotein complex required for chromosomal DNA replication in budding yeast. Takayama, Y., Kamimura, Y., Okawa, M., Muramatsu, S., Sugino, A., Araki, H. Genes Dev. (2003) [Pubmed]
A CDK-catalysed regulatory phosphorylation for formation of the DNA replication complex Sld2-Dpb11. Tak, Y.S., Tanaka, Y., Endo, S., Kamimura, Y., Araki, H. EMBO J. (2006) [Pubmed]
DRC1, DNA replication and checkpoint protein 1, functions with DPB11 to control DNA replication and the S-phase checkpoint in Saccharomyces cerevisiae. Wang, H., Elledge, S.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
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. Araki, H., Leem, S.H., Phongdara, A., Sugino, A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
Genetic and physical interactions between DPB11 and DDC1 in the yeast DNA damage response pathway. Wang, H., Elledge, S.J. Genetics (2002) [Pubmed]
Dpb11, the budding yeast homolog of TopBP1, functions with the checkpoint clamp in recombination repair. Ogiwara, H., Ui, A., Onoda, F., Tada, S., Enomoto, T., Seki, M. Nucleic Acids Res. (2006) [Pubmed]
Sld2, which interacts with Dpb11 in Saccharomyces cerevisiae, is required for chromosomal DNA replication. Kamimura, Y., Masumoto, H., Sugino, A., Araki, H. Mol. Cell. Biol. (1998) [Pubmed]
Yeast DNA replication protein Dpb11 activates the Mec1/ATR checkpoint kinase. Navadgi-Patil, V.M., Burgers, P.M. J. Biol. Chem. (2008) [Pubmed]
CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast. Tanaka, S., Umemori, T., Hirai, K., Muramatsu, S., Kamimura, Y., Araki, H. Nature (2007) [Pubmed]
CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damage. Reid, R.J., Fiorani, P., Sugawara, M., Bjornsti, M.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]

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AGOS_AFR095C	Ashbya gossypii ATCC 10895
KLLA0F14300g	Kluyveromyces lactis NRRL Y-1140

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