Cyclin a is required for the onset of DNA replication in mammalian fibroblasts

Girard, F; Strausfeld, U.; Fernandez, Anne; Lamb, Ned

doi:10.1016/0092-8674(91)90293-8

Cited by 821 publications

(308 citation statements)

References 42 publications

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“…Therefore, both the timing of B-Myb modi®cation during S-phase and its relative e cacy suggest that cyclin A/Cdk2 is the enzyme responsible in vivo. Previously it has been shown that cyclin A expression is mandatory for the onset and maintenance of DNA synthesis in mammalian cells (Girard et al, 1991;Pagano et al, 1992). As cyclin A was found to synergise with B-Myb to promote cells into S-phase (Figure 6), it will be of interest to explore further the possibility that the requirement for cyclin A for DNA synthesis re¯ects, at least in part, enhancement of B-Myb by direct phosphorylation.…”

Section: Discussionmentioning

confidence: 95%

B-Myb function can be markedly enhanced by cyclin A-dependent kinase and protein truncation

1997

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Section: Discussionmentioning

confidence: 95%

B-Myb function can be markedly enhanced by cyclin A-dependent kinase and protein truncation

1997

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“…The loss of this activity, which is essential for S phase traverse (Girard et al, 1991;Pagano et al, 1992;Resnitzky et al, 1995;Walker and Maller, 1991), could provide a basis to explain the rapid cessation of DNA synthesis observed in primary cells. As shown in Figure 5a, we found that the decrease in cyclin A kinase activity in MK cells closely resembled that observed in primary keratinocytes, signi®cantly decreasing between 3 ± 6 h in suspension.…”

Section: Resultsmentioning

confidence: 99%

Primary keratinocytes have an adhesion dependent S phase checkpoint that is absent in immortalized cell lines

1998

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In order to understand the mechanism through which loss of anchorage inhibits growth, we have investigated the events that occur in murine keratinocytes upon substratum detachment utilizing both primary cells and established immortalized cell lines. Our data has revealed that while both primary and immortalized cells undergo growth arrest in suspension, the nature of this arrest is markedly di erent. Primary cells exhibit a growth arrest that is characterized by rapid cessation of DNA synthesis resulting in a static S phase population. In contrast, an immortalized non-tumorgenic cell line, Balb MK, exhibits growth arrest as measured by thymidine incorporation, but does not prevent cells that have entered S phase from continuing into G 2 /M, and accumulating as a 4N population. In contrast to both primary and MK cells, the tumorigenic SLC-1 cell line did not accumulate in a speci®c cell cycle interval and were able to undergo continuous growth in suspension. Examination of cyclin A protein and its associated activity revealed that cyclin A protein levels decreased in primary but not MK cells; suggesting the continued presence of cyclin A may allow continued DNA synthesis observed in MK cells. Furthermore, we demonstrate the accumulation of suspension cultured MK cells as a 4N population correlated with the loss of cyclin A/cdk2 kinase activity, which in turn occurred through the accumulation of p27 kip1 , whereas neither p27 kip1 accumulation nor loss of cyclin A activity was observed in SLC-1 cells. Our results clearly reveal that the process of growth inhibition in suspension cultured cells may occur in several forms with distinct characteristics that are dependent on the status of cyclin/cdk complexes and CKI proteins. Tumor derived cells in suspension did not lose cyclin A dependent kinase activity and thus continued to grow and divide.

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“…This is compatible with the fact that megakaryocytes proceed through a complete G2 phase before entering mitosis. It is also expected that to undergo S phase, cells have to express cyclin A, as it has been established for proliferating cells (Ohtsubo et al, 1995;Zindy et al, 1992;Girard et al, 1991). Surprisingly, though, in other re-replicating systems including mouse trophoblasts (MacAuley et al, 1998;Sprenger et al, 1997), cyclin A appears not to be needed for extra S phases.…”

Section: Discussionmentioning

confidence: 99%

Ectopic expression of cyclin E allows non-endomitotic megakaryoblastic K562 cells to establish re-replication cycles

et al. 2000

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Megakaryocytes become polyploid by entering a truncated cell cycle, consisting of alternate S phases and abortive mitoses. We have investigated the regulation of the G1/S transition by comparing two megakaryoblastic cell lines, HEL and K562, which respectively do or do not become polyploid in response to phorbol esters. A pronounced downregulation of cyclin A, and to a lesser extent of cyclin E, occurred in K562 cells during the ®rst 24 h after TPA treatment, in contrast with re-replicating HEL cells, in which both cyclins were present in individual G2/M cells. Transactivation experiments suggested that the absence of cyclin A in di erentiated K562 cells could be due to a TPA-mediated inhibition of its transcription. To investigate the potential role of cyclin E in the establishment of re-replication cycles, we isolated K562 clones constitutively expressing cyclin E. The resulting clones, and also K562 cells transiently expressing cyclin E, entered re-replication cycles when treated with TPA. The transcriptional activity of the cyclin A promoter was not inhibited after TPA treatment, and although the levels of cyclin A¯uctuated during further re-replication cycles, they never decreased below S phase levels. We conclude that the presence of cyclin E in megakaryoblastic G2/M cells determines cyclin A expression and allows the entrance into an extra S phase.

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Cyclin a is required for the onset of DNA replication in mammalian fibroblasts

Cited by 821 publications

References 42 publications

B-Myb function can be markedly enhanced by cyclin A-dependent kinase and protein truncation

B-Myb function can be markedly enhanced by cyclin A-dependent kinase and protein truncation

Primary keratinocytes have an adhesion dependent S phase checkpoint that is absent in immortalized cell lines

Ectopic expression of cyclin E allows non-endomitotic megakaryoblastic K562 cells to establish re-replication cycles

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