Regulation of DNA replication during development

Abstract

SummaryAs development unfolds, DNA replication is not only coordinated with cell proliferation, but is regulated uniquely in specific cell types and organs. This differential regulation of DNA synthesis requires crosstalk between DNA replication and differentiation. This dynamic aspect of DNA replication is highlighted by the finding that the distribution of replication origins varies between differentiated cell types and changes with differentiation. Moreover, differential DNA replication in some cell types can lead to increases or decreases in gene copy number along chromosomes. This review highlights the recent advances and technologies that have provided us with new insights into the developmental regulation of DNA replication.

Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells

“…Differential replication is a phenomenon common to all Drosophila polytene and polyploid tissues (8). Before this study, however, it was not known whether mammalian cells that become polyploid also change gene copy number in parts of the genome.…”

“…In Drosophila endocycles, differential DNA replication occurs, rather than an integral doubling of the genome during S phase (8). This can lead to increased gene copy number, gene amplification, of specific genomic regions, as occurs at six sites in ovarian follicle cells (9).…”

p27Kip1participates in the regulation of endoreplication in differentiating chick retinal ganglion cells

“…While the C value increases during S-phase, remaining duplicated during G2, the N value remains unaltered as the cell progresses through the cell cycle. [10][11][12][13] Polyploidy, defined as the presence in the cell nucleus of more than 2 sets of chromosomes, can affect all the cells of the organism. In this case, it is referred to as germinal polyploidy.…”

“…27 Endoreplication represents a major mechanism leading to developmental programmed somatic polyploidy. [10][11][12] This process consists of successive rounds of DNA synthesis in the absence of mitosis (endocycles), thus leading to cells with a DNA content higher than 2C. Although the mechanism of endoreplication is far from being completely understood, it seems to be dependent on the levels and activity of the Cdk/Cyclin complex after the completion of every S phase, the oscillations of Cyclin E and Geminin levels, and the localization of the minichromosome maintenance protein complexes.…”

“…Although the mechanism of endoreplication is far from being completely understood, it seems to be dependent on the levels and activity of the Cdk/Cyclin complex after the completion of every S phase, the oscillations of Cyclin E and Geminin levels, and the localization of the minichromosome maintenance protein complexes. [10][11][12]28 Endoreplication can be mimicked by inhibition of Cdk1 activity, 11 and the subsequent prevention of the mitotic process. Moreover, cyclin E/Cdk2 is the G1 Cdk complex crucial for DNA synthesis initiation during the endoreplicative process.…”