There is published evidence to establish a causal relationship between estrogens in the environment and breast cancer. However, there are serious gaps in our knowledge about estrogen levels in the environment and a call is required for a world wide effort to provide more data on many more samples sites. Of the data available, the synthetic estrogen, ethinyl estradiol, is more persistent in the environment than natural estrogens and may be a greater cause for environmental concern. Finally, we believe that there is an urgent requirement for inter-disciplinary studies of estrogens in order to better understand their ecological and environmental impact.

When Xenopus eggs and egg extracts replicate DNA, replication origins are positioned randomly with respect to DNA sequence. However, a completely random distribution of origins would generate some unacceptably large interorigin distances. We have investigated the distribution of replication origins in Xenopus sperm nuclei replicating in Xenopus egg extract. Replicating DNA was labeled with [3H]thymidine or bromodeoxyuridine and the geometry of labeled sites on spread DNA was examined. Most origins were spaced 5–15 kb apart. This regular distribution provides an explanation for how complete chromosome replication can be ensured although origins are positioned randomly with respect to DNA sequence. Origins were grouped into small clusters (typically containing 5–10 replicons) that fired at approximately the same time, with different clusters being activated at different times in S phase. This suggests that a temporal program of origin firing similar to that seen in somatic cells also exists in the Xenopus embryo. When the quantity of origin recognition complexes (ORCs) on the chromatin was restricted, the average interorigin distance increased, and the number of origins in each cluster decreased. This suggests that the binding of ORCs to chromatin determines the regular spacing of origins in this system.

The effects of ascorbate (ASC) and dehydroascorbate (DHA) on cell proliferation were examined in the tobacco Bright Yellow 2 (TBY-2) cell line to test the hypothesis that the ASC-DHA pair is a specific regulator of cell division. The hypothesis was tested by measuring the levels of ASC and DHA or another general redox pair, glutathione (GSH) and glutathione disulfide (GSSG), during the exponential-growth phase of TBY-2 cells. A peak in ASC, but not GSH, levels coincided with a peak in the mitotic index. Moreover, when the cells were enriched with ascorbate, a stimulation of cell division occurred whereas, when the cells were enriched with DHA, the mitotic index was reduced. In contrast, glutathione did not affect the mitotic-index peak during this exponential-growth phase. The data are consistent in showing that the ASC-DHA pair acts as a specific redox sensor which is part of the mechanism that regulates cell cycle progression in this cell line.

The basic components of the plant cell cycle are G1 (postmitotic interphase), S-phase (DNA synthesis phase), G2 (premitotic interphase) and mitosis/cytokinesis. Proliferating cells are phosphoregulated by cyclin-dependent protein kinases (CDKs). Plant D-type cyclins are sensors of the G0 to G1 transition, and are also important for G2/M. At G1/S, the S-phase transcription factor, 'E2F', is released from inhibitory retinoblastoma protein. Negative regulation of G1 events is through KRPs (Kip-related proteins). Plant S-phase genes are similar to animal ones, but timing of expression can be different (e.g. CDC6 at the start of S-phase) and functional evidence is limited. At G2/M, A-type and the unique B-type CDKs when bound to A, B and D cyclins, drive cells into division; they are negatively regulated by ICK1/2 and perhaps also by WEE1 kinase. In Arabidopsis , a putative CDC25 lacks a regulatory domain. Mitosis depends on correct temporal activity of CDKs, Aurora kinases and anaphase promotion complex; CDK-cyclin B activity beyond metaphase is catastrophic. Endoreduplication (re-replication of DNA in the absence of mitosis) is characterized by E2F expression and down-regulation of mitotic cyclins. Some cell size data support, whilst others negate, the idea of cell size having an impact on development.New Phytologist (2007) 174 : [261][262][263][264][265][266][267][268][269][270][271][272][273][274][275][276][277][278]

DNA replication is identified as a rate limiting step in the cell cycle, the flexibility of DNA replication is explored, and we speculate on how the licensing of initiation points of DNA replication may be a responsive component of the positive nucleotypic effect of C-value on the duration of the mitotic cell cycle.