Molecular system ensuring genomic inheritance through successive generations

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Molecular mechanisms that ensure genomic inheritance through successive generations have been studied, based on the cell cycle control and the nuclear formation. Our findings are summarized below.1. Meiotic cell cycle progression : Almost complete signaling pathway that leads to meiotic reinitiation in starfish oocytes has been revealed to be composed of the putative receptor for maturation-inducing hormone, 1-MeAde / Gβ1γ2 / I-β type PI3-kinase / PDK1 and putative PDK2 / Akt (PKB) / Cdc2-cyclin B / Plk1. After meiotic reinitiation, p90Rsk is activated immediately downstream of the Mos-MAPK pathway to regulate positively both meiosis I to II transition and G1-phase arrest after completion of meiosis II.2. Formation of male and female pronuclei : Cell-free extracts derived from Xenopus oocytes or eggs were utilized to analyze these processes. Upon fertiliztion, NAP1 functions as a molecular chaperone for histone H1 at the chromatin remodeling in sperm nuclei. During oocyte maturation, the ability of nuclear import that depends on importin α is accelerated, and the LI-type nuclear lamin is newly synthesized, possibly providing a clue to understand how the ability for nuclear formation is acquired in this period.3. Initiation of S-phase upon fertilization : In unfertilized mature eggs of starfish, MCMs are already loaded onto chromatin in female pronucleus, but the loading of Cdc45, which allows the loading of DNA polymerase a to DNA, is prevented downstream of the Mos-MAPK-p90Rsk pathway. Abolishment of p90Rsk activity is sufficient for initiation of DNA replication, thus providing a clue to answer the classic question in biology how fertilization initiates S-phase.