Cytoplasmic poly(A) polymerases mediate cellular responses to S phase arrest

Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12079-84. doi: 10.1073/pnas.192467799. Epub 2002 Sep 6.

Abstract

The S-M checkpoint delays mitosis until DNA replication is complete; cells defective in this checkpoint lose viability when DNA replication is inhibited. This inviability can be suppressed in fission yeast by overexpression of Cid1 or the related protein Cid13. Fission yeast contain six cid1/cid13-like genes, whereas budding yeast has just two, TRF4 and TRF5. Trf4 and Trf5 were recently reported to comprise an essential DNA polymerase activity required for the establishment of sister chromatid cohesion. In contrast, we find that Cid1 is not a DNA polymerase but instead uses RNA substrates and has poly(A) polymerase activity. Unlike the previously characterized yeast poly(A) polymerase, which is a nuclear enzyme, Cid1 and Cid13 are constitutively cytoplasmic. Cid1 has a degree of substrate specificity in vitro, consistent with the notion that it targets a subset of cytoplasmic mRNAs for polyadenylation in vivo, hence increasing their stability and/or efficiency of translation. Preferred Cid1 targets presumably include mRNAs encoding components of the S-M checkpoint, whereas Cid13 targets are likely to be involved in dNTP metabolism. Cytoplasmic polyadenylation is known to be an important regulatory mechanism during early development in animals. Our findings in yeast suggest that this level of gene regulation is of more general significance in eukaryotic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Checkpoint Kinase 2
  • Cytoplasm / enzymology
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Genes, Fungal
  • Hydroxyurea / pharmacology
  • Mitosis / drug effects
  • Mitosis / physiology
  • Molecular Sequence Data
  • Mutation
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Polynucleotide Adenylyltransferase / genetics
  • Polynucleotide Adenylyltransferase / metabolism*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • S Phase / drug effects
  • S Phase / physiology*
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / drug effects
  • Schizosaccharomyces / enzymology
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Substrate Specificity

Substances

  • Cell Cycle Proteins
  • Fungal Proteins
  • Recombinant Proteins
  • Schizosaccharomyces pombe Proteins
  • Protein Kinases
  • Checkpoint Kinase 2
  • rad3 protein, S pombe
  • Cid13 protein, S pombe
  • Polynucleotide Adenylyltransferase
  • Phosphoprotein Phosphatases
  • Hydroxyurea

Associated data

  • SWISSPROT/Q9UT49