SPK1 is an essential S-phase-specific gene of Saccharomyces cerevisiae that encodes a nuclear serine/threonine/tyrosine kinase.

Zheng, Pan; Fay, David S.; Burton, Janet L.; Xiao, Hong; Pinkham, Jennifer L.; Stern, David F.

doi:10.1128/mcb.13.9.5829

Cited by 101 publications

(85 citation statements)

References 53 publications

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“…Similar results were obtained for Hhp2. On the basis of this behavior (Kuret and Schulman, (Zheng et al, 1993). Hhpl was examined in these experiments.…”

Section: Resultsmentioning

confidence: 99%

“…The Mcklp gene product is important for yeast kinetochore function in mitosis and for early meiotic gene expression (Neigeborn and Mitchell, 1991;Shero and Hieter, 1991). The Spklp protein kinase is an essential S-phase-specific gene product that is a nuclear Ser/Thr/Tyr kinase (Zheng et al, 1993). It is suggested that Spklp plays an important role in regulating DNA synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a number of protein kinases that phosphorylate both at Tyr and at Ser/Thr (so called "dual-specificity" enzymes) have been described . In S. cerevisiae, examples of these enzymes include Mcklp and Spklp (Dailey et al, 1990, Stern et al, 1991Lim et al, 1993, Zheng et al, 1993. Although the gene structure and classical characterization of CKI activity has revealed that CKI is most closely related to serine/ threonine protein kinases, several experiments have suggested that CKI might have a promiscuous substrate specificity.…”

Section: Introductionmentioning

confidence: 99%

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Budding and fission yeast casein kinase I isoforms have dual-specificity protein kinase activity.

Hoekstra

Dhillon

Carmel

et al. 1994

MBoC

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We have examined the activity and substrate specificity of the Saccharomyces cerevisiae Hrr25p and the Schizosaccharomyces pombe Hhpl, Hhp2, and Ckil protein kinase isoforms. These four gene products are isotypes of casein kinase I (CKI), and the sequence of these protein kinases predicts that they are protein serine/threonine kinases. However, each of these four protein kinases, when expressed in Escherichia coli in an active form, was recognized by anti-phosphotyrosine antibodies. Phosphoamino acid analysis of 32P-labeled proteins showed phosphorylation on serine, threonine, and tyrosine residues. The E. coli produced forms of Hhpl, Hhp2, and Ckil were autophosphorylated on tyrosine, and both Hhpl and Hhp2 were capable of phosphorylating the tyrosine-protein kinase synthetic peptide substrate polymer poly-E4Yl. Immune complex protein kinases assays from S. pombe cells showed that Hhpl-containing precipitates were associated with a protein-tyrosine kinase activity, and the Hhpl present in these immunoprecipitates was phosphorylated on tyrosine residues. Although dephosphorylation of Hhpl and Hhp2 by Ser/Thr phosphatase had little effect on the specific activity, tyrosine dephosphorylation of Hhpl and Hhp2 caused a 1.8-to 3.1-fold increase in the Km for poly-E4Y, and casein. These data demonstrate that four different CKI isoforms from two different yeasts are capable of protein-tyrosine kinase activity and encode dual-specificity protein kinases.

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“…Similar results were obtained for Hhp2. On the basis of this behavior (Kuret and Schulman, (Zheng et al, 1993). Hhpl was examined in these experiments.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Budding and fission yeast casein kinase I isoforms have dual-specificity protein kinase activity.

Hoekstra

Dhillon

Carmel

et al. 1994

MBoC

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“…The family of proteins containing FHA domains, which includes proteins of diverse functional roles, is growing rapidly. Examples of the FHA family include: Dun1 and Rad53 (or Spk1), which are involved in DNA damage repair and the S phase checkpoint in Saccharomyces cerevisiae (Allen et al, 1994;Navas et al, 1995;Sun et al, 1998;Zheng et al, 1993); Cds1, the Schizosaccharomyces pombe homolog of Rad53 (Murakami & Okayama, 1995); Mek1, which is related to meitotic recombination of yeast (Leem & Ogawa, 1992); KAPP, kinase-associated protein phosphatase from Arobidopsis thaliana, which binds to the receptorlike protein kinase RLK5 (Stone et al, 1994); and Ki-67, a human nuclear protein related to cell proliferation (Schluter et al, 1993). The two most recent members are HuCds1 (or Chk2) in humans (Brown et al, 1999;Matsuoka et al, 1998), and Dmnk in Drosophila melanogaster (Oishi et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Structure and function of a new phosphopeptide-binding domain containing the FHA2 of rad53

Liao

Byeon

Tsai

1999

Journal of Molecular Biology

109

120

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“…The RAD53 gene also contains two similar cis-acting-elements in its promoter that up-regulate its expression at late G1-/S-phase [17]. Cell-cycle regulation of Rad53 may be important for S-phase specific inhibition of Sml1 to release RNR activity during a normal S-phase.…”

Section: Discussionmentioning

confidence: 99%

Checkpoint deficient rad53-11 yeast cannot accumulate dNTPs in response to DNA damage

Koç

Merrill

2007

Biochemical and Biophysical Research Communications

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Deoxyribonucleotide pools are maintained at levels that support efficient and yet accurate DNA replication and repair. Rad53 is part of a protein kinase regulatory cascade that, conceptually, promotes dNTP accumulation in four ways: (1) it activates the transcription of ribonucleotide reductase subunits by inhibiting the Crt1 repressor; (2) it plays a role in relocalization of ribonucleotide reductase subunits RNR2 and RNR4 from nucleus to cytoplasm; (3) it antagonizes the action of Sml1, a protein that binds and inhibits ribonucleotide reductase; and (4) it blocks cell-cycle progression in response to DNA damage, thus preventing dNTP consumption through replication forks. Although several lines of evidence support the above modes of Rad53 action, an effect of a rad53 mutation on dNTP levels has not been directly demonstrated. In fact, in a previous study, a rad53-11 mutation did not result in lower dNTP levels in asynchronous cells or in synchronized cells that entered the S-phase in the presence of the RNR inhibitor hydroxyurea. These anomalies prompted us to investigate whether the rad53-11 mutation affected dNTP levels in cells exposed to a DNA-damaging dose of ethylmethyl sulfonate (EMS). Although dNTP levels increased by 2-to 3-fold in EMS treated wild-type cells, rad53-11 cells showed no such change. Thus, the results indicate that Rad53 checkpoint function is not required for dNTP pool maintenance in normally growing cells, but is required for dNTP pool expansion in cells exposed to DNA-damaging agents. Ó 2006 Elsevier Inc. All rights reserved.Keywords: Rad53; dNTP; DNA damage; RNR; EMS; Yeast Cells have evolved mechanisms to maintain or augment deoxyribonucleotide triphosphate levels during DNA synthesis and repair. Yeast cells respond to DNA damage and replication block by arresting the progression of the cell cycle at specific points and by inducing the expression of genes thought to facilitate DNA repair. These responses are mediated by a kinase cascade that appears to be conserved among eukaryotes. Two essential genes, MEC1 and RAD53, are central players in the kinase cascade that leads to cell-cycle arrest at all the checkpoints and transcriptional activation in response to DNA damage. Cells with mutations in the Mec1 or Rad53 genes are defective in both cell-cycle arrest and gene expression responses in response to DNA damage, but retain their essential functions for cell survival under normal conditions [1][2][3][4][5]. Among the best characterized transcriptional targets of the Rad53 kinase cascade are the RNR genes, which encode subunits of ribonucleotide reductase, the enzyme that catalyzes the rate-limiting step in dNTP synthesis [1]. In addition to transcriptional induction of RNR genes, the Rad53 pathway also induces RNR activity through the removal of Sml1, an RNR inhibitor that binds to large subunits and inhibits enzyme activity [6]. Lethality of Rad53 null mutation is suppressed by overexpression of genes encoding ribonucleotide reductase [3] or by deletion of RNR inhibitor Sml1...

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SPK1 is an essential S-phase-specific gene of Saccharomyces cerevisiae that encodes a nuclear serine/threonine/tyrosine kinase.

Cited by 101 publications

References 53 publications

Budding and fission yeast casein kinase I isoforms have dual-specificity protein kinase activity.

Budding and fission yeast casein kinase I isoforms have dual-specificity protein kinase activity.

Structure and function of a new phosphopeptide-binding domain containing the FHA2 of rad53

Checkpoint deficient rad53-11 yeast cannot accumulate dNTPs in response to DNA damage

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