Schizosaccharomyces pombe Mop1-Mcs2 is related to mammalian CAK.
The cyclin-dependent kinase (CDK)-activating kinase, CAK, from mammals and amphibians consists of MO15/CDK7 and cyclin H, a complex which has been identified also as a RNA polymerase II C-terminal domain (CTD) kinase. While the Schizosaccharomyces pombe cdc2 gene product also requires an activating phosphorylation, the enzyme responsible has not been identified. We have isolated an essential S.pombe gene, mop1, whose product is closely related to MO15 and to Saccharomyces cerevisiae Kin28. The functional similarity of Mop1 and MO15 is reflected in the ability of MO15 to rescue a mop1 null allele. This suggests that Mop1 would be a CDK, and indeed Mop1 associates with a previously characterized cyclin H-related cyclin Mcs2 of S.pombe. Also, Mop1 and Mcs2 can associate with the heterologous partners human cyclin H and MO15, respectively. Moreover, the rescue of a temperature-sensitive mcs2 strain by expression of mop1+ demonstrates a genetic interaction between mop1 and mcs2. In a functional assay, immunoprecipitated Mop1-Mcs2 acts both as an RNA polymerase II CTD kinase and as a CAK. The CAK activity of Mop1-Mcs2 distinguishes it from the related CDK-cyclin pair Kin28-Ccl1 from S.cerevisiae, and supports the notion that Mop1-Mcs2 may represent a homolog of MO15-cyclin H in S.pombe with apparent dual roles as a RNA polymerase CTD kinase and as a CAK.
Damagnez
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Mitotix Inc., Cambridge, MA 02139, USA.
Mäkelä
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Cottarel
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D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D056748:Cyclin H; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D016213:Cyclins / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D005800:Genes, Fungal; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014170:Transformation, Genetic; D000095043:Cyclin-Dependent Kinase-Activating Kinase
C534751:CCNH protein, human; D056748:Cyclin H; D016213:Cyclins; D018076:DNA, Complementary; D004271:DNA, Fungal; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase