FIGURE 2.

Expression profiles of cell cycle checkpoint and DNA repair proteins in the brain. (A,B) Relative mRNA expression levels of checkpoint and DNA repair proteins in cerebral cortices of mice at E10, E18, and 2 months old. See the legend of Figure 1 for the quantitative real-time PCR method. Each Y-axis shows the mean ratio ± standard deviation (SD). Significance of differences between E10 and E18 or 2 months old was determined by applying Student’s t test. *P < 0.05, **P < 0.01, ***P < 0.001, and n.s., no significant difference. Schematic illustration depicting alternative functions of DNA repair and cell cycle proteins in neural progenitors (C) and differentiated neurons (D). In proliferating neural progenitors, cell cycle and DNA repair proteins basically function in the nucleus. In differentiated neurons, some of these nuclear proteins, such as p27^Kip1 and ATM, relocate to the cytoplasm and show extra-cell cycle/DNA repair-regulatory functions, including the regulation of neuronal cytoskeleton, in post-mitotic neurons. While p27^Kip1 is associated with neuronal cytoskeleton, ATM and ATR control clathrin-mediated endocytosis in excitatory and inhibitory synapses, respectively. Centrosomal Aurora A and synaptic cyclin E are reported to control neuronal migration and synapse plasticity, respectively. BRCA2 may interact with Filamin A. It is also possible that DNA double-strand breaks may have a role in cytoskeletal regulation via LINC (linkers of the nucleoskeleton to the cytoskeleton) complex (see the text for details).