Big flies, small repeats: the "Thr-Gly" region of the period gene in Diptera

The region of the clock gene period (per) that encodes a repetitive tract of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran species both within and outside the Drosophilidae. All the non- Drosophilidae sequences in this region are short and present a remarkably stable picture compared to the Drosophilidae, in which the region is much larger and extremely variable, both in size and composition. The accelerated evolution in the repetitive region of the Drosophilidae appears to be mainly due to an expansion of two ancestral repeats, one encoding a Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and asparagine or threonine. In some drosophilids the expansion involves a duplication of the pentapeptide sequence, but in Drosophila pseudoobscura both the dipeptide and the pentapeptide repeats are present in larger numbers. In the nondrosophilids, however, the pentapeptide sequence is represented by one copy and the dipeptide by two copies. These observations fulfill some of the predictions of recent theoretical models that have simulated the evolution of repetitive sequences.      

Precocious G1/S transitions and genomic instability: the origin connection

Both in yeast and in higher eukaryotes, genomic instability often ensues when the G1/S transition machinery is deregulated and cells are forced to enter S phase prematurely. This case of acquired mutability is particularly important, since a majority of genes mutated in human cancers encode factors that influence the G1/S transition. The precocious G1/S transition often results in a sub-optimal S phase. Moreover, the problems generated in such an S phase can escape detection by the cellular surveillance systems, allowing undeterred mitosis. This review focuses primarily on budding yeast data, where progress has been made in the past couple of years towards a mechanistic understanding of the underlying processes. A dual surveillance system is discussed, which relies on the presence of licensed but unfired origins and stalled replication forks to deter mitosis until replication is complete. Normally, this dual surveillance system allows S phase to be flexible in duration in a variety of growth conditions, when the fork density and/or fork progression rates can vary widely. However, precocious exit from G1 can have a disabling effect on this surveillance system. Premature exit from G1 can cut short the licensing of origins and the accumulation of resources for the upcoming replication, while giving a cell a false indication that it is metabolically ready to conduct S phase.