A novel family of TRF (DNA topoisomerase I-related function) genes required for proper nuclear segregation.
We recently reported the identification of a gene, TRF4 (for DNA topoisomerase related function), in a screen for mutations that are synthetically lethal with mutations in DNA topoisomerase I (top1). Here we describe the isolation of a second member of the TRF4 gene family, TRF5. Overexpression of TRF5 complements the inviability of top1 trf4 double mutants. The predicted Trf5 protein is 55% identical and 72% similar to Trf4p. As with Trf4p, a region of Trf5p is homologous to the catalytically dispensable N-terminus of Top1p. The TRF4/5 function is essential as trf4 trf5 double mutants are inviable. A trf4 (ts) trf5 double mutant is hypersensitive to the anti-microtubule agent thiabendazole at a semi-permissive temperature, suggesting that TRF4/5 function is required at the time of mitosis. Examination of nuclear morphology in a trf4 (ts) trf5 mutant at a restrictive temperature reveals the presence of many cells undergoing aberrant nuclear division, as well as many anucleate cells, demonstrating that the TRF4/5 function is required for proper mitosis. Database searches reveal the existence of probable Schizosaccharomyces pombe and human homologs of Trf4p, indicating that TRF4 is the canonical member of a gene family that is highly conserved evolutionarily.
Castaño
I B
IB
Department of Radiation Oncology, University of California, San Francisco, CA 94143, USA.
Heath-Pagliuso
S
S
Sadoff
B U
BU
Fitzhugh
D J
DJ
Christman
M F
MF
D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000502:physiology*; D004264:DNA Topoisomerases, Type I / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005816:Genetic Complementation Test; D016681:Genome, Fungal; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D004264:DNA Topoisomerases, Type I