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We discuss novel insight into the role and consequences of the phosphorylation of the translation initiation factor eIF2α in the context of stress responses and cell-cycle regulation. eIF2α is centrally located to regulate translation and its phosphorylation in response to different environmental challenges is one of the best characterized stress-response pathways. In addition to its role in stress management, eIF2α phosphorylation is also linked to cell-cycle progression and memory consolidation in the nervous system. The best known consequences of eIF2α phosphorylation are downregulation of global translation and stimulation of translation of some mRNAs. However, recent evidence shows that (i) eIF2α phosphorylation is not always required for the downregulation of global translation after exposure to stress and (ii) eIF2α phosphorylation does not necessarily lead to the downregulation of global translation. These results suggest that the textbook view of eIF2α phosphorylation needs to be revised and that there must be additional regulatory mechanisms at play. [ABSTRACT FROM AUTHOR]

Controversial decisions to ban athletes and the Russian doping scandal have raised doubts about the reliability of doping controls in professional sports. To ensure fairness and due process, doping tests must be transparent and adhere to the best scientific standards. [ABSTRACT FROM AUTHOR]

Cdt1 is an essential protein required for licensing of replication origins. Here, we show that in Schizosaccharomyces pombe, Cdt1 is proteolysed in M and G1 phases in response to DNA damage and that this mechanism seems to be conserved from yeast to Metazoa. This degradation does not require Rad3 and Cds1, indicating that it is independent of classic DNA damage and replication checkpoint pathways. Damage-induced degradation of Cdt1 is dependent on Cdt2 and Ddb1, which are components of a Cul4 ubiquitin ligase. We also show that Cdt2 and Ddb1 are needed for cell-cycle changes in Cdt1 levels in the absence of DNA damage. Cdt2 and Ddb1 have been shown to be involved in the degradation of the Spd1 inhibitor of ribonucleotide reductase after DNA damage, and we speculate that Cdt1 downregulation might contribute to genome stability by reducing demand on dNTP pools during DNA repair. [ABSTRACT FROM AUTHOR]

In order to multiply, both prokaryotic and eukaryotic cells go through a series of events that are collectively called the cell cycle. However, DNA replication, mitosis and cell division may also be viewed as having their own, in principle independent, cycles, which are tied together by mechanisms extrinsic to the cell cycle-the checkpoints -that maintain the order of events. We propose that our understanding of cell-cycle regulation is enhanced by viewing each event individually, as an independently regulated process. The nature of the parameters that regulate cell-cycle events is discussed and, in particular, we argue that cell mass is not such a parameter. [ABSTRACT FROM AUTHOR]

The article focuses on chromosome replication to cell division. The replicon model continues to provide a fruitful framework for the exploration of increasingly complex and transacting regulatory elements. A general problem for the cell is how to ensure that all chromosome segments are replicated once per cell cycle, but not twice. Eukaryotic origins are normally licensed for initiation as the cells exit mitosis. The regulation of replicator usage in eukaryotes and the timing of firing are influenced by the developmental stage of the organism, the differentiation state of the cell, gene expression, DNA damage and the perturbation of replication fork progression.

In Esdierichia coli cells, the origin of chromosomal replication is temporarily inactivated after initiation has occurred. Origin sequestration is the first line of defence against over-initiation, providing a time window during which the initiation potential can be reduced by: (i) titration of DnaA proteins to newly replicated chromosomal elements; (ii) regulation of the activity of the DnaA initiator protein; and (iii) sequestration of the dnaA gene promoter. This review represents the first attempt to consider together older and more recent data on such inactivation mechanisms in order to analyze their contributions to the overall tight replication control observed in vivo. All cells have developed mechanisms for origin inactivation, but those of other bacteria and eukaryotic cells are clearly distinct from those of L coli. Possible differences and similarities are discussed. [ABSTRACT FROM AUTHOR]