Identification of Clb2 Residues Required for Swe1 Regulation of Clb2-Cdc28 in <i>Saccharomyces cerevisiae</i>

Hu, Fangfang; Gan, Yan; Aparicio, Oscar M.

doi:10.1534/genetics.108.086611

Cited by 20 publications

(17 citation statements)

References 47 publications

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“…Although the hydrophobic patch residues are essential for Clb5 function, it is not clear whether the hydrophobic patch alone is sufficient to explain the differences in substrate specificity between different cyclins. The HP motif in Clb1 and Clb2 imposes regulation of the cyclin-Cdk complexes by allowing interaction with Swe1, which regulates Cdk1 activity (Hu et al 2008). However, it is unclear whether the HP motif in these cyclins influences their substrate specificity.…”

mentioning

confidence: 99%

Among B-Type Cyclins Only CLB5 and CLB6 Promote Premeiotic S Phase in Saccharomyces cerevisiae

Decesare

Stuart

2012

Genetics

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The Saccharomyces cerevisiae cyclin Clb5 is required for premeiotic S phase, meiotic recombination, and successful progression through meiosis. Clb5 is not essential for mitotic proliferation because Clb1-Clb4 can support DNA replication in clb5 clb6 mutants. Clb1, Clb3, and Clb4 accumulate in clb5 clb6 cells during meiotic differentiation yet fail to promote premeiotic DNA replication. When expressed under the regulation of the CLB5 promoter, Clb1 and Clb3 accumulate and are active in the early stages of meiotic differentiation but cannot induce premeiotic DNA replication, suggesting that they do not target Cdk1 to the necessary substrates. The Clb5 hydrophobic patch (HP) residues are important for Clb5 function but this motif alone does not provide the specificity required for Clb5 to induce premeiotic S phase. Domain exchange experiments demonstrated that the amino terminus of Clb5 when fused to Clb3 confers upon Clb3 the ability to induce premeiotic S phase. Chimeric cyclins containing smaller regions of the Clb5 amino terminus displayed reduced ability to activate premeiotic DNA replication despite being more abundant and having greater associated histone H1 kinase activity than endogenous Clb5. These observations suggest that Clb5 has a unique ability to trigger premeiotic S phase and that the amino-terminal region of Clb5 contributes to its specificity and regulates the functions performed by the cyclin-Cdk complex.

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mentioning

confidence: 99%

Among B-Type Cyclins Only CLB5 and CLB6 Promote Premeiotic S Phase in Saccharomyces cerevisiae

Decesare

Stuart

2012

Genetics

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“…We observed instead that the absence of Clb2 resulted in a strong reduction in the level of phospho-Y19 Cdc28, a result that is consistent with previous studies revealing a preferential targeting of Clb2-bound CDK by Swe1 under unperturbed conditions. 37,38 Taken together, these results rule out the possibility that Swe1-mediated inhibition of the remaining Clb-CDKs causes the aberrant DNA damage response of clb2Δ mutants.…”

Section: The Aberrant Response Of Clb2δ Cells Is Men- Apc- and Swe1mentioning

confidence: 63%

Spatially distinct functions of Clb2 in the DNA damage response

et al. 2013

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“…These data indicate that Clb5 is the cyclin that activates Cdk1 for Sum1 phosphorylation. Cyclins influence whether Cdk1 is subject to checkpoint-mediated inactivation by the Swe1 inhibitory kinase, and the Clb5-bound form of Cdk1 is insensitive to Swe1 (37,38). These findings therefore provide an explanation for why the phosphorylation of Sum1 by Cdk1 is not inhibited by the recombination checkpoint.…”

Section: Resultsmentioning

confidence: 85%

Multisite Phosphorylation of the Sum1 Transcriptional Repressor by S-Phase Kinases Controls Exit from Meiotic Prophase in Yeast

Corbi

Sunder

Weinreich

et al. 2014

Molecular and Cellular Biology

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Activation of the meiotic transcription factor Ndt80 is a key regulatory transition in the life cycle of Saccharomyces cerevisiae because it triggers exit from pachytene and entry into meiosis. The NDT80 promoter is held inactive by a complex containing the DNA-binding protein Sum1 and the histone deacetylase Hst1. Meiosis-specific phosphorylation of Sum1 by the protein kinases Cdk1, Ime2, and Cdc7 is required for NDT80 expression. Here, we show that the S-phase-promoting cyclin Clb5 activates Cdk1 to phosphorylate most, and perhaps all, of the 11 minimal cyclin-dependent kinase (CDK) phospho-consensus sites (S/T-P) in Sum1. Nine of these sites can individually promote modest levels of meiosis, yet these sites function in a quasiadditive manner to promote substantial levels of meiosis. Two Cdk1 sites and an Ime2 site individually promote high levels of meiosis, likely by preparing Sum1 for phosphorylation by Cdc7. Chromatin immunoprecipitation reveals that the phosphorylation sites are required for removal of Sum1 from the NDT80 promoter. We also find that Sum1, but not its partner protein Hst1, is required to repress NDT80 transcription. Thus, while the phosphorylation of Sum1 may lead to dissociation from DNA by influencing Hst1, it is the presence of Sum1 on DNA that determines whether NDT80 will be expressed.

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Identification of Clb2 Residues Required for Swe1 Regulation of Clb2-Cdc28 in Saccharomyces cerevisiae

Cited by 20 publications

References 47 publications

Among B-Type Cyclins Only CLB5 and CLB6 Promote Premeiotic S Phase in Saccharomyces cerevisiae

Among B-Type Cyclins Only CLB5 and CLB6 Promote Premeiotic S Phase in Saccharomyces cerevisiae

Spatially distinct functions of Clb2 in the DNA damage response

Multisite Phosphorylation of the Sum1 Transcriptional Repressor by S-Phase Kinases Controls Exit from Meiotic Prophase in Yeast

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