1986
DOI: 10.1128/mcb.6.10.3463-3469.1986
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Induction, by Thymidylate Stress, of Genetic Recombination as Evidenced by Deletion of a Transferred Genetic Marker in Mouse FM3A Cells

Abstract: Studies were made on the genetic consequences of methotrexate-directed thymidylate stress, focusing attention on a human thymidylate synthase gene that was introduced as a heterologous genetic marker into mouse thymidylate synthase-negative mutant cells. Thymidylate stress induced thymidylate synthase-negative segregants with concomitant loss of human thymidylate synthase activity with frequencies 1 to 2 orders of magnitude higher than the uninduced spontaneous level in some but not all transformant lines. Ind… Show more

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“…This suggests that regulation of TS mRNA primarily occurs at the post-transcriptional level in human and mouse cells undergoing growth stimulation. The half-life of poly(A)+ TS mRNA is approximately 8 h in both resting and growing mouse cells [ 37 , 38 , 39 ], suggesting that mRNA stability regulation is not a critical factor. Thus, TS mRNA dysregulation profoundly affects cell proliferation and apoptosis, potentially leading to abnormalities in vascular endothelial cells and compromised blood vessel function.…”
Section: Discussionmentioning
confidence: 99%
“…This suggests that regulation of TS mRNA primarily occurs at the post-transcriptional level in human and mouse cells undergoing growth stimulation. The half-life of poly(A)+ TS mRNA is approximately 8 h in both resting and growing mouse cells [ 37 , 38 , 39 ], suggesting that mRNA stability regulation is not a critical factor. Thus, TS mRNA dysregulation profoundly affects cell proliferation and apoptosis, potentially leading to abnormalities in vascular endothelial cells and compromised blood vessel function.…”
Section: Discussionmentioning
confidence: 99%