Nucleic Acids Research, Vol 24, Issue 12 2404-2410, Copyright © 1996 by Oxford University Press
IB Castano, S Heath-Pagliuso, BU Sadoff, DJ Fitzhugh and MF Christman
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.
ARTICLES
A novel family of TRF (DNA topoisomerase I-related function) genes required for proper nuclear segregation
Department of Radiation Oncology, University of California, San Francisco, CA 94143, USA.
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