Chromosome Condensation

Abstract

During meiosis, the replicated chromatids remain condensed, which is important to prevent inappropriate DNA replication and to allow proper progression through the second meiotic cell cycle. Di Agostino et al. examined meiosis stimulated by the phosphatase inhibitor okadaic acid in mouse spermatocytes. Entry into meiosis as detected by chromatin condensation was stimulated by OA, and this could be inhibited by pretreatment of the spermatocytes with the mitogen-activated protein kinase (MAPK) inhibitor U0126. One of the downstream effectors of MAPK is the kinase p90Rsk. Spermatocytes, which are meiosis competent, expressed the p90Rsk2 isoform, whereas mitotic spermatids expressed p90Rsk3. Various assays demonstrated that p90Rsk2 was phosphorylated and activated by OA treatment of spermatocytes and that activation was blocked by exposure to the MAPK inhibitor. Furthermore, like the MAPKs, ERK1 and ERK2, p90Rsk2 was physically associated with the condensed chromatin in the meiotic cells. Histone 3 is phosphorylated in condensed chromatin, and although p90Rsk2 can phosphorylate histone 3 in vitro, the exposure of the spermatocytes to U0126 did not prevent OA-stimulated histone 3 phosphorylation. Thus, histone 3 phosphorylation correlates with chromatin condensation, but is not sufficient to cause condensation. Di Agonstino et al. found that p90Rsk2 activated the NIMA (never in mitosis in Aspergillus nidulan s)-like kinase Nek2 and the stimulation of Nek2 was inhibited in OA treated spermatocyes pretreated with U0126. If histone phosphorylation by p90Rsk2 is not the relevant target for triggering chromatin condensation, then possibly Nek2 represents the important downstream effector of p90Rsk2. The authors propose that a kinase complex forms on the chromosomes that include ERK1 and ERK2, p90Rsk2, and Nek2 and that this complex is responsible for triggering chromatin condensation in response to extracellular signals. S. Di Agostino, P. Rossi, R. Geremia, C. Sette, The MAPK pathway triggers activation of Nek2 during chromosome condensation in mouse spermatocytes. Development 129 , 1715-1727 (2002). [Online Journal]