DNA replication in mammalian cells in the presence of cycloheximide

Gautschi, J.R.; Kern, Renée

doi:10.1016/0014-4827(73)90270-x

Cited by 92 publications

(25 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Total histone synthesis recovered after 1 h to the same level as DNA synthesis, and then the two levels of synthesis rose more slowly together. Such initial differences in the extent of inhibition of DNA and histone synthesis at growth-arresting concentrations of cycloheximide have been reported previously (1,8,24). Our results indicate that this difference can also exist at growthpermitting concentrations of cycloheximide (see below).…”

supporting

confidence: 88%

“…A possible reason for this can be seen in Fig. 3D; the rate of DNA synthesis initially is not inhibited as much as the rate of protein synthesis, and as the rate of histone synthesis rises, the two rates become much closer after 1 h. The finding that some DNA replication continues even when protein synthesis is almost completely inhibited has been documented widely (1,8,24). These results (Fig.…”

mentioning

confidence: 62%

“…On the other hand it has been shown that inhibition of protein synthesis immediately leads to an almost proportional inhibition of DNA synthesis (8). Considering that most histone and DNA syntheses are known to be coupled, these * Corresponding author.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mechanism for differential sensitivity of the chromosome and growth cycles of mammalian cells to the rate of protein synthesis.

Wu¹,

Bonner²

1985

Mol. Cell. Biol.

View full text Add to dashboard Cite

It has been docuiliented widely that when the generation times of eucaryotic cells are lengthened by slowing the rate of protein synthesis, the duration of the chromosotne cycle (S, G2, and M phases) remains relatively invariant. Paradoxically, when the growth of exponentially growing cultures of CHO cells is partially inhibited with inhibitors of protein synthesis, the immediate effect is a proportionate reduction in the rate of total protein, histone protein, and DNA synthesis. However, on -further investigation it was found that over the next 2 h the rates of histone protein and DNA synthesis recover, in some cases completely to the uninhibited rate, while the synthesis rates of other proteins do. not recover. We called this process chromosome cycle compensation. The amount of compensation seen in CHO cell cultures can account quantitatively for the relative invariance in the length of the chromosome cycle (S, G2, and M phases) reported for these cells. The mechanism for this compensation involves a specific increase in the levels of histone mRNAs. An invariant chromosome cycle coupled with a lengthening growth cycle must result in a disproportionate lengthening of the GI phase. Thus, these results suggest that chromosome cycle invariance may be due more to specific cellular compensation mechanisms rather than to the more usual interpretation involving a rate-limiting step for cell cycle progression in the Gl phase.When inhibitors of protein synthesis are added to cultures of exponentially growing cells, their doubling time lengthens approximately in proportion to the decreased rate of protein synthesis. With moderate inhibition of protein synthesis, almost all of the lengthening occurs in the G1 interval while the S, G2, and M intervals, named collectively by Mitchison (17) as the DNA division or chromosome cycle, are relatively unaffected (14,15,19,20,21). Rossow et al. (21) studied a Swiss 3T3 cell line which grew with a doubling time of about 16 h, 4 h in the G1 phase and 12 h in the chromosome cycle (S, G2, and M phases). When the rate of protein synthesis in this culture was inhibited to about 35% of the control rate by the addition of cycloheximide, the doubling time increased to about 63 h with a greatly increased G1 phase of about 47 h but only a slightly increased chromosome cycle of 16 h. Liskay et al. (14) have studied the Chinese hamster cell line V79-8 which had no measurable G1 interval; the chromosome cycle of 9.2 h accounted for the doubling time. When the rate of protein synthesis in these cultures was inhibited to 60% that of the control, their doubling times increased to 14.2 h with a G1 phase of 4.2 h but only a slightly increased chromosome cycle of 10.2 h. A relative invariance for the chromosome cycle has also been reported for yeasts (11) and other fungi (16). These results are commonly interpreted in terms of a step just before the S phase, usually in the G1 phase, which is rate limiting for cell cycle progression and which is particularly sensitive to the rate of protein synthesis ...

show abstract

supporting

confidence: 88%

mentioning

confidence: 62%

See 1 more Smart Citation

Mechanism for differential sensitivity of the chromosome and growth cycles of mammalian cells to the rate of protein synthesis.

Wu¹,

Bonner²

1985

Mol. Cell. Biol.

View full text Add to dashboard Cite

show abstract

“…Cells which were allowed to synthesize protein during the first 6 hr after slicing (phase I) could synthesize DNA at 20% of the rate in cells in control discs even when later protein synthesis was almost completely blocked by CH, while cells which were synthesizing DNA at a certain instance needed continuous synthesis of protein during 6 to 8 hr immediately prior to the instance to synthesize DNA at a full rate (phase II). Events (8,23). By analyzing the chain elongation rate of DNA strands, the reduction of the rate of DNA synthesis in the presence of CH was shown to be resulted from a reduced rate of chain elongation.…”

Section: Discussionmentioning

confidence: 99%

“…By analyzing the chain elongation rate of DNA strands, the reduction of the rate of DNA synthesis in the presence of CH was shown to be resulted from a reduced rate of chain elongation. The existence of proteins with a short half-life which regulate the chain elongation rate of DNA strand has been suggested (8,23 …”

Section: Discussionmentioning

confidence: 99%

Induction of Deoxyribonucleic Acid Synthesis in Potato Tuber Slices

Watanabe¹,

Imaseki²

1976

Plant Physiol.

View full text Add to dashboard Cite

Timing of protein synthesis which is a prerequisite to DNA synthesis induced in potato tuber tissue (Solanum tuberosum L.) by cut injury has been studied using cycloheximide. The induction of DNA synthesis which was measured by incorporation of 3H-thymidine was completely inhibited when the inhibitor was applied to the tuber discs immediately after slicing. When the application of cycloheximide was delayed for 6 hours or more after slcing, DNA synthesis was observed but its rate was reduced to 20% of control. The inhibitory effect of cycloheximide, however, rapidly decreased when the inhibitor was applied at 6 or less hours immediately prior to determination of DNA synthesis. (1,10). RNA and protein syntheses were reported to be involved in the development of wound respiration in potato tuber slices and the necessary protein was synthesized in a very

show abstract

Ordered replication of DNA sequences: Synthesis of mouse satellite and adjacent main band sequences

Dooley¹,

Ozer²

1979

Journal Cellular Physiology

View full text Add to dashboard Cite

The replication of mouse satellite DNA was delayed when synchronized 3T3 cells were exposed to low concentrations of hydroxyurea during S phase, It appears that the onset of satellite replication is not a time dependent event, but instead requires that a certain amount of main band DNA be synthesized first. Using hydroxyapatite chromatography and S1 nuclease digestion, a procedure was developed to quantitate the synthesis of both satellite and neighboring main band sequences. The replication kinetics of satellite determined by this method agree with previous estimates. Main band sequences adjacent to satellite appear to replicate in concert with satellite DNA. The results are discussed and related to the limitations of the techniques utilized.

show abstract

DNA replication in mammalian cells in the presence of cycloheximide

Cited by 92 publications

References 26 publications

Mechanism for differential sensitivity of the chromosome and growth cycles of mammalian cells to the rate of protein synthesis.

Mechanism for differential sensitivity of the chromosome and growth cycles of mammalian cells to the rate of protein synthesis.

Induction of Deoxyribonucleic Acid Synthesis in Potato Tuber Slices

Ordered replication of DNA sequences: Synthesis of mouse satellite and adjacent main band sequences

Contact Info

Product

Resources

About