The <i>Schizosaccharomyces pombe spo6</i><sup>+</sup> gene encoding a nuclear protein with sequence similarity to budding yeast Dbf4 is required for meiotic second division and sporulation

Nakamura, Toshio; Kishida, Masao; Shimoda, Chikashi

doi:10.1046/j.1365-2443.2000.00343.x

Cited by 40 publications

(51 citation statements)

References 57 publications

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“…2A). These motifs are conserved not only in known Cdc7 regulatory subunits but also in Spo6, another Dbf4-related molecule in fission yeast, the function of which is specific for sporulation (29).…”

Section: The Hsk1 Kinase Attenuated Mutant Hsk1k129r-k130smentioning

confidence: 99%

Bipartite Binding of a Kinase Activator Activates Cdc7-related Kinase Essential for S Phase

Ogino

Takeda

Matsui

et al. 2001

Journal of Biological Chemistry

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Saccharomyces cerevisiae CDC7 is a temperature-sensitive mutant defective in initiation of DNA replication (1). Initial experiments indicated that ongoing protein synthesis was not required for completion of the S phase once the function of Cdc7 was executed (2, 3). dbf4 (dumbbell former), isolated from independent screening (4), showed terminal phenotypes similar to those of cdc7(ts). Later, DBF4 was re-isolated as a multicopy suppressor of cdc7(ts) (5). Subsequent genetic and biochemical evidence showed that DBF4 encodes a regulatory or activation subunit for Cdc7 protein (6).Structural and functional homologues of Cdc7 have been noted in fission yeast, human, mouse, and Xenopus (7-10). The kinase domains are particularly well conserved and identity between yeast and human is 45%. Activation subunits for these Cdc7-related kinases have been isolated through interaction screening or in data base searches (11-17). Expression of the activation subunit is cell cycle-regulated and is accumulated during the S phase (13,(17)(18)(19)(20)(21). Accordingly, Cdc7-dependent kinase activity is high during the S phase. Despite functional similarity to cyclins in apparent periodic appearance and kinase activation during the cell cycle, Dbf4 and cyclins share no apparent sequence similarity. Compared with the Cdc7 catalytic subunits, Dbf4 and activation subunits for Cdc7-related kinases from other eukaryotes are more diverged. There is less than 25% identity between Dbf4 and Dfp1/Him1, the fission yeast homologue of Dbf4, and no overall homology was evident between yeast and mammalian Dbf4 homologues. However, alignment of known Dbf4 homologues revealed two stretches of amino acids (Dbf4 motif N and Dbf4 motif C) conserved in all the known Dbf4/Him1-related molecules (13). We discovered another stretch of amino acids (Dbf4 motif M),which is also conserved in all the Dbf4-related molecules (22).With fission yeast Dfp1/Him1 protein as a model, we have now generated a series of deletion and point mutants and examined the functions of these conserved motifs of Dbf4-related molecules regarding in vivo functions, binding to the catalytic subunit, kinase activation, and interaction with replication origins. We describe here essential functions of Dbf4 motif M and Dbf4 motif C for mitotic cell cycle and kinase activation and the potential of each motif to serve as an independent Hsk1 binding module. The combination of these two motifs can activate the kinase activity of Hsk1. We also found that Dbf4 motif N, related to BRCA C-terminal domain motif although not essential for mitotic function and kinase activation, plays crucial roles in the DNA replication checkpoint as well as in recovery from DNA damageinduced cell cycle arrest and may be involved in interaction with replication machinery or chromatin. EXPERIMENTAL PROCEDURESYeast Strains, Media, and Genetics-Schizosaccharomyces pombe strains were grown in rich (YES) or minimal (EMM) 1 medium containing the required supplements. General genetic manipulation (23) and

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Section: The Hsk1 Kinase Attenuated Mutant Hsk1k129r-k130smentioning

confidence: 99%

Bipartite Binding of a Kinase Activator Activates Cdc7-related Kinase Essential for S Phase

Ogino

Takeda

Matsui

et al. 2001

Journal of Biological Chemistry

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“…This complex is often referred to as DDK (Dbf4-dependent kinase). The existence in fission yeast of a Cdc7/Dbf4 complex paralog, Spo4/Spo6, and the recent discovery of multiple Dbf4-related molecules in animal cells suggest that they belong to a novel DDK protein kinase family (7)(8)(9)(10). Functional differences between family members have started to emerge but they need to be further characterized.…”

mentioning

confidence: 99%

Xenopus CDC7/DRF1 Complex Is Required for the Initiation of DNA Replication

Silva

Bradley

Gao

et al. 2006

Journal of Biological Chemistry

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The Cdc7 kinase is essential for the initiation of DNA replication in eukaryotes. Two regulatory subunits of the Xenopus Cdc7 kinase have been identified: XDbf4 and XDrf1. In this study we determined the expression pattern of XDbf4 and XDrf1 and examined their involvement in DNA replication. We show that XDrf1 expression is restricted to oogenesis and early embryos, whereas XDbf4 is expressed throughout development. Immunodepletion from Xenopus egg extracts indicated that both proteins are only found in complexes with XCdc7 and there is a 5-fold molar excess of the XCdc7/Drf1 over SCdc7/Dbf4 complexes. Both complexes exhibit kinase activity and are differentially phosphorylated during the cell cycle. Depletion of the XCdc7/Drf1 from egg extracts inhibited DNA replication, whereas depletion of XCdc7/Dbf4 had little effect. Chromatin binding studies indicated that XCdc7/Drf1 is required for pre-replication complex activation but not their assembly. XCdc7/Dbf4 complexes bound to the chromatin in two steps: the first step was independent of pre-replication complex assembly and the second step was dependent on pre-replication complex activation. By contrast, binding of XCdc7/Drf1 complexes was entirely dependent on pre-replication complex assembly. Finally, we present evidence that the association of the two complexes on the chromatin is not regulated by ATR checkpoint pathways that result from DNA replication blocks. These data suggest that Cdc7/Drf1 but not Cdc7/Dbf4 complexes support the initiation of DNA replication in Xenopus egg extracts and during early embryonic development.In eukaryotes, initiation of DNA replication requires the assembly and activation of pre-replication complexes (pre-RCs) 5 on chromatin (1). Sequential binding to DNA of the origin recognition complex, Cdc6, Cdt1, and mini-chromosome maintenance proteins (Mcm2-7) lead to formation of pre-RCs. Pre-RC activation is under the control of two kinases, Cdk2 and Cdc7, and ultimately results in the loading of replication factors such as Cdc45 and the unwinding of replication origins by the MCM helicase complex (2-5).Cdc7 is a serine/threonine kinase that is conserved from yeast to human and is essential for cell proliferation and embryonic development (6). Like CDKs (cyclin-dependent kinases), Cdc7 activity is regulated by its association with a regulatory subunit, the Dbf4 protein. This complex is often referred to as DDK (Dbf4-dependent kinase). The existence in fission yeast of a Cdc7/Dbf4 complex paralog, Spo4/Spo6, and the recent discovery of multiple Dbf4-related molecules in animal cells suggest that they belong to a novel DDK protein kinase family (7-10

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“…Whereas the signals and factors that positively regulate rem1 and other middle meiotic genes in fission yeast have been extensively investigated (Horie et al 1998;Abe and Shimoda 2000;Nakamura et al 2000;Watanabe et al 2001;Okuzaki et al 2003;Nakamura et al 2004;Malapeira et al 2005;Nakamura et al 2005;Ogino and Masai 2006;Mata et al 2007;Murakami-Tonami et al 2007;Moldon et al 2008;Nakase et al 2009), only three published reports have focused on negative regulation (Shimoseki and Shimoda 2001;Averbeck et al 2005;Chen et al 2012), and none of these examined polyadenylation. In the earliest, splicing of transcripts from the mes1 gene was shown to occur even in vegetative cells when a secondary structure in the 59 UTR was disrupted (Shimoseki and Shimoda 2001).…”

Section: Shifting Paradigms For Negative Regulation Of Middle Meioticmentioning

confidence: 99%

A dominant role for meiosis-specific 3′ RNA processing in controlling expression of a fission yeast cyclin gene

Potter

Cremona

Sunder

et al. 2012

RNA

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Meiotic gene regulation provides a rich source of insight into mechanisms of temporal control during development. We previously reported that accumulation of many meiotic mRNAs in fission yeast is governed by changes in 39 RNA processing and elucidated the molecular basis of this regulatory mechanism for an early meiotic gene. Here, we report that cleavage/polyadenylation is also the nexus of negative control for middle meiotic genes. Parallel profiles of splicing and polyadenylation are observed over a meiotic time course for both rem1 and spo4 but not for a constitutive control gene. Nevertheless, polyadenylation of rem1 transcripts is restricted to meiosis by a splicing-independent mechanism. Through systematic sequence substitutions, we identified a negative control region (NCR) located upstream of the rem1 transcription start site and found that it is required to block 39 RNA processing in proliferating cells. Ablation of the NCR relieves inhibition regardless of whether the intron is present, absent, or carries splice site mutations. Consistent with the previous report of a polypeptide encoded by the first exon of rem1, we discovered a second 39 processing site just downstream from the 59 splice site. Polyadenylation within the intron is activated concurrent with the downstream site during meiosis, is controlled by the NCR, and is enhanced when splicing is blocked via 59 junction or branch point mutations. Taken together, these data suggest a novel regulatory mechanism in which a 59 element modulates the dynamic interplay between splicing and polyadenylation.

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The Schizosaccharomyces pombe spo6⁺ gene encoding a nuclear protein with sequence similarity to budding yeast Dbf4 is required for meiotic second division and sporulation

Abstract: Background: Sporulation of the ®ssion yeast Schizosaccharomyces pombe is a cell differentiation process which accompanies meiosis. The spo6 gene was identi®ed as a sporulation-speci®c gene, whose transcription was regulated by the forkhead family transcription factor Mei4.

Cited by 40 publications

References 57 publications

Bipartite Binding of a Kinase Activator Activates Cdc7-related Kinase Essential for S Phase

Bipartite Binding of a Kinase Activator Activates Cdc7-related Kinase Essential for S Phase

Xenopus CDC7/DRF1 Complex Is Required for the Initiation of DNA Replication

A dominant role for meiosis-specific 3′ RNA processing in controlling expression of a fission yeast cyclin gene

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The Schizosaccharomyces pombe spo6+ gene encoding a nuclear protein with sequence similarity to budding yeast Dbf4 is required for meiotic second division and sporulation

Abstract: Background: Sporulation of the ®ssion yeast Schizosaccharomyces pombe is a cell differentiation process which accompanies meiosis. The spo6 gene was identi®ed as a sporulation-speci®c gene, whose transcription was regulated by the forkhead family transcription factor Mei4.

Cited by 40 publications

References 57 publications

Bipartite Binding of a Kinase Activator Activates Cdc7-related Kinase Essential for S Phase

Bipartite Binding of a Kinase Activator Activates Cdc7-related Kinase Essential for S Phase

Xenopus CDC7/DRF1 Complex Is Required for the Initiation of DNA Replication

A dominant role for meiosis-specific 3′ RNA processing in controlling expression of a fission yeast cyclin gene

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Product

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The Schizosaccharomyces pombe spo6⁺ gene encoding a nuclear protein with sequence similarity to budding yeast Dbf4 is required for meiotic second division and sporulation