A temperature-sensitive mutation in asparaginyl-tRNA synthetase causes cell-cycle arrest in early S phase.
The Chinese hamster temperature-sensitive cell-cycle mutant ts24 was analyzed biochemically in order to determine the nature of this lesion. The inability of these cells to proceed through S phase at the restrictive temperature could be complemented by the addition of asparagine to the growth medium, and enzymological analysis showed that this line contains a temperature-sensitive asparaginyl-tRNA synthetase. Normal asparaginyl-tRNA synthetase activity was restored in cells transfected with cloned genomic DNA that overcomes the mutational defect. In corroboration with these results it was shown that a different temperature-sensitive asparaginyl-tRNA synthetase mutant isolated in another laboratory was blocked in S phase in a manner similar to that of ts24. While the mechanism by which asparaginyl-tRNA synthetase affects cell-cycle progression has not been elucidated, it can be shown that it is not mediated through alteration in overall levels of protein synthesis.
Diamond
G
G
Department of Genetics and Cellular Biochemistry, Hebrew University, Jerusalem, Israel.
Cedar
H
H
Marcus
M
M
D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics*; D000818:Animals; D001226:Aspartate-tRNA Ligase; D002453:Cell Cycle; D002460:Cell Line; D006224:Cricetinae; D004261:DNA Replication; D005434:Flow Cytometry; D007399:Interphase; D009154:Mutation; D012346:RNA, Transfer, Amino Acyl; D013696:Temperature
D012346:RNA, Transfer, Amino Acyl; D000604:Amino Acyl-tRNA Synthetases; D001226:Aspartate-tRNA Ligase; C029194:asparaginyl-tRNA synthetase