Initiate then elongate

In This Issue In This Issue Initiate then elongate tudies on yeast have provided significant insights into eukaryotic DNA replication, but it has been difficult to examine the process in more complex organisms. On page 225, Claycomb et al. have taken advantage of a peculiar aspect of insect biology to develop a new model for studying metazoan DNA replication, and have already made one surprising finding with the system. During a specific period of oocyte development in Drosophila , the ovarian follicle cells surrounding the oocyte begin to amplify several defined clusters of genes. Using real-time PCR S DUP/Cdt1 (red) functions near replication origins (green, top), but also during elongation (bottom). and a combination of microscopy techniques, the authors discovered that this amplification occurs stepwise. First, initiation takes place at the loci that will be amplified, and then, in a separate developmental stage, the replication forks elongate. The natural separation of initiation and elongation provides an ideal model for studying both processes. The system has already helped uncover one apparent difference between yeast and fly systems. The DUP/Cdt1 protein, which is thought to act only during initiation in yeast, travels with the elongating replication forks in Drosophila. Claycomb et al. are now hoping to determine how this and other metazoan replication factors are regulated in vivo. ᭿ eurofilaments modulate the shape and size of neurons. On page 279, Rao et al. describe several lines of evidence demonstrating that neurofilaments interact with the motor protein myosin Va, and that this interaction is critical for proper neurofilament organization. Besides illuminating a poorly understood aspect of neuronal biology, the findings may also help explain the pathogenesis of a debilitating human genetic disease. In both humans and mice, mutations in the myosin Va gene cause severe defects in skin pigmentation and fatal convulsive disorders. Combining biochemical and genetic approaches, the authors found that the neurofilament light chain is a major ligand of myosin Va in mouse nervous tissue. In mice lacking functional myosin Va, neuro-filaments in axons are more densely packed than they are in wild-type mice. The results suggest that proper neurofilament spacing, and hence normal neuronal shape and function, depends on the dynamic cross-linking of neurofilaments and micro-filaments by myosin Va. Myosin Va might also provide the motive force to move membrane-associated enzymes and receptors along neurofilaments, and to carry out the short-range rearrangements of neurofilaments within the axon that occur during …