Endoreduplication (also referred to as endoreplication or endocycling) is replication of the nuclear genome in the absence of mitosis, which leads to elevated nuclear gene content and polyploidy. Endoreduplication can be understood simply as a variant form of the mitotic cell cycle (G1-S-G2-M) in which mitosis is circumvented entirely, due to modulation of cyclin-dependent kinase (CDK) activity.[ While endoreduplication is often limited to specific cell types in animals, it is considerably more widespread in plants, such that can be detected in the majority of plant tissues.]
Examples in nature
Endoreduplicating cell types that have been studied extensively in model organisms
Endoreduplication, endomitosis and polytenization
Endoreduplication, endomitosis and polytenization are three different processes resulting in polyploidization of a cell in a regulated manner. In endoreduplication cells skip Mitosis completely by exiting the mitotic cell cycle in the G2 phase after completing the S phase several times, resulting in a mononucleated polyploid cell. The cell ends up with twice as many copies of each chromosome per repeat of the S phase.
Biological significance
Based on the wide array of cell types in which endoreduplication occurs, a variety of hypotheses have been generated to explain the functional importance of this phenomenon.[ Unfortunately, experimental evidence to support these conclusions is somewhat limited.
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Cell differentiation
In developing plant tissues the transition from mitosis to endoreduplication often coincides with cell differentiation and morphogenesis.
Cell/organism size
Cell ploidy often correlates with cell size,[ and in some instances, disruption of endoreduplication results in diminished cell and tissue size ]
Oogenesis and embryonic development
Endoreduplication is commonly observed in cells responsible for the nourishment and protection of oocytes and embryos. It has been suggested that increased gene copy number might allow for the mass production of proteins required to meet the metabolic demands of embryogenesis and early development.[ Consistent with this notion, mutation of the Myc oncogene in Drosophila follicle cells results in reduced endoreduplication and abortive oogenesis.]
Buffering the genome
Another hypothesis is that endoreduplication buffers against DNA damage and mutation because it provides extra copies of important genes.[ However, this notion is purely speculative and there is limited evidence to the contrary. For example, analysis of polyploid yeast strains suggests that they are more sensitive to radiation than diploid strains.]
Stress response
Research in plants suggests that endoreduplication may also play a role in modulating stress responses. By manipulating expression of E2fe (a repressor of endocycling in plants), researchers were able to demonstrate that increased cell ploidy lessens the negative impact of drought stress on leaf size.
Genetic control of endoreplication
The best-studied example of a mitosis-to-endoreduplication transition occurs in Drosophila follicle cells and is activated by Notch signaling.
Entry into S-phase during endoreduplication (and mitosis) is regulated through the formation of a prereplicative complex (pre-RC) at replication origins, followed by recruitment and activation of the DNA replication machinery. In the context of endoreduplication these events are facilitated by an oscillation in cyclin E-Cdk2 activity. Cyclin E-Cdk2 activity drives the recruitment and activation of the replication machinery,[ The mechanism by which cyclin E-Cdk2 inhibits pre-RC formation involves downregulation of APC-Cdh1-mediated proteolysis and accumulation of the protein Geminin, which is responsible for sequestration of the pre-RC component Cdt1.]
Oscillations in Cyclin E-Cdk2 activity are modulated via transcriptional and post-transcriptional mechanisms. Expression of cyclin E is activated by E2F transcription factors that were shown to be required for endoreduplication.
Premeiotic endomitosis in unisexual vertebrates
The unisexual salamanders (genus Ambystoma) are the oldest known unisexual vertebrate lineage, having arisen about 5 million years ago.
