title: A mutation in the largest (catalytic) subunit of RNA polymerase II and its relation to the arrest of the cell cycle in G(1) phase.
abstract: Transcriptional activity of RNA polymerase II is modulated during the cell cycle. We previously identified a temperature-sensitive mutation in the largest (catalytic) subunit of RNA polymerase II (RPB1) that causes cell cycle arrest and genome instability. We now characterize a different cell line that has a temperature-sensitive defect in cell cycle progression, and find that it also has a mutation in RPB1. The temperature-sensitive mutant, tsAF8, of the Syrian hamster cell line, BHK21, arrests at the non-permissive temperature in the mid-G(1) phase. We show that RPB1 in tsAF8--which is found exclusively in the nucleus at the permissive temperature--is also found in the cytoplasm at the non-permissive temperature. Comparison of the DNA sequences of the RPB1 gene in the wild-type and mutant shows the mutant phenotype results from a (hemizygous) C-to-A variation at nucleotide 944 in one RPB1 allele; this gives rise to an ala-to-asp substitution at residue 315 in the protein. Aligning the amino acid sequences from various species reveals that ala(315) is highly conserved in eukaryotes.
authors.affiliation: Genome Research Group, National Institute of Radiological Sciences, 4-9-1, Anagawa, Chiba, 263-8555, Japan. k_sugaya@nirs.go.jp
authors.forename: K
authors.initials: K
authors.lastname: Sugaya
authors.forename: S
authors.initials: S
authors.lastname: Sasanuma
authors.forename: P R
authors.initials: PR
authors.lastname: Cook
authors.forename: K
authors.initials: K
authors.lastname: Mita
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D020134:Catalytic Domain / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D016193:G1 Phase / Q000235:genetics / Q000502:physiology*; D005838:Genotype; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013696:Temperature
chemical_list: D018076:DNA, Complementary; D012319:RNA Polymerase II