13 Changes in DNA Replication during Animal Development

Abstract

Throughout animal growth and development, the cell cycle is modified in response to developmental signals. These alterations in the cell cycle influence the control of S phase and the properties of DNA replication (outlined in Table 1). The production of haploid gametes requires a modified cell cycle, meiosis, in which two rounds of chromosome segregation follow a single S phase. Thus, S phase must be prevented between the two meiotic divisions. In the early embryos of many animals, a rapid cell cycle occurs in which S phase oscillates with mitosis without gap phases. This S-M cycle necessitates unique controls for the entry into S phase. Later in embryogenesis in Drosophila and Xenopus, a G₁ phase is added to the cell cycle, resulting in another developmental alteration of the onset of S phase. There are numerous examples of tissues that become polytene as a consequence of a modified cell cycle with only an S phase and a gap phase.

These developmental changes in the cell cycle require special controls for entry into S phase. The regulation of the onset of S phase has been extensively investigated in the normal cell cycle with G₁-S-G₂-M phases and is reviewed by Nasymth (this volume) and Weisshart and Fanning (this volume). Cyclin-dependent kinases (cyclin-cdk complexes), including cyclins E, D, and A complexed with cdk2, 4, and 6, are all known to play a role in S-phase regulation of higher eukaryotes (Sherr 1993Sherr 1994). G₁ cyclin kinases are thought to phosphorylate the retinoblastoma gene product, pRb,...