Molecular control and function of endoreplication in development and physiology

Endoreplication, also called endoreduplication, is a cell cycle variant of multicellular eukaryotes in which mitosis is skipped and cells repeatedly replicate their DNA, resulting in cellular polyploidy. In recent years, research results have shed light on the molecular mechanism of endoreplication control, but the function of this cell-cycle variant has remained elusive. However, new evidence is at last providing insight into the biological relevance of cellular polyploidy, demonstrating that endoreplication is essential for developmental processes, such as cell fate maintenance, and is a prominent response to physiological conditions, such as pathogen attack or DNA damage. Thus, endoreplication is being revealed as an important module in plant growth that contributes to the robustness of plant life. Endoreplication, also called endoreduplication, is a cell cycle variant of multicellular eukaryotes in which mitosis is skipped and cells repeatedly replicate their DNA, resulting in cellular polyploidy. In recent years, research results have shed light on the molecular mechanism of endoreplication control, but the function of this cell-cycle variant has remained elusive. However, new evidence is at last providing insight into the biological relevance of cellular polyploidy, demonstrating that endoreplication is essential for developmental processes, such as cell fate maintenance, and is a prominent response to physiological conditions, such as pathogen attack or DNA damage. Thus, endoreplication is being revealed as an important module in plant growth that contributes to the robustness of plant life. Anaphase-Promoting Complex/Cyclosome. A highly specialized E3 ubiquitin protein ligase that targets proteins containing a destruction (D)-box sequence. Primary targets include cell cycle regulators, in particular the mitotic A- and B-type cyclins. Ortholog of Cdh1 in mammals and fungi, and of Fzr in Drosophila, acting as an activator of the APC/C. Plants possess two distinct types of CCS52 genes: CCS52A, which apparently controls cell division and onset of endoreduplication, and CCS52B, for which no clear function has been assigned yet. CDK-activating phosphatase that controls entry into mitosis in animals and fungi, thereby counteracting the WEE1 kinase; however this phosphatase is absent in plants. Cyclin-dependent kinase. This conserved serine/threonine-specific kinase regulates the cell cycle transitions through phosphorylation of key substrates and needs cyclin binding to be active. A-type CDK produced throughout the cell cycle and required for both the G1-to-S and G2-to-M transition points. B-type CDK. Plant-specific class of CDKs that are activated during G2/M and are required for progression through mitosis. Two subfamilies exist, CDKB1 and CDKB2. CDKB1 genes are expressed early in the cell cycle, starting during DNA replication and continuing into M phase, whereas CDKB2 expression is more strictly confined to G2/M. CDK inhibitors. These regulators of CDK activity arrest cell cycle progression in response to developmental and environmental signals. Plants possess two types of CKI, i.e. the KRP/ICK and the SIM/SMR families. Cyclin. They bind and activate CDKs and are often produced in a cell cycle phase-dependent manner. A-type cyclin that controls S-phase progression and the G2-to-M transition. It is targeted by the APC/C for destruction. B-type cyclin that regulates the G2-to-M transition and progression through mitosis. It is targeted by the APC/C for destruction. D-type cyclin that responds to mitogenic stimuli, thereby linking the environment and intracellular signaling pathways with cell cycle progression. Destruction Box. The sequence motif (RxxLxxIxN) marks a protein for ubiquitination by the APC/C, targeting it for degradation by the ubiquitin proteasome system. DP/E2F-like proteins that are structurally related to E2F/DP transcription factors. They operate in dividing cells as repressors of differentiation events, including endoreplication and cell expansion. Heterodimeric transcription factors that control the expression of genes required for DNA replication. F-box-like 17 that is part of a SCF E3 ubiquitin protein ligase complex that targets KRP/ICK proteins for destruction. KIP-RELATED PROTEIN/INTERACTOR OF CDKs. This plant-specific class of CKIs targets CDKA for inhibition and controls developmental aspects of the cell cycle, including gametogenesis, lateral root initiation, and endoreduplication. RETINOBLASTOMA-RELATED 1 (RBR1) protein, homolog of the human tumor suppressor Rb. Rb has many different functions, among the most important for cell cycle regulation is the binding to and thereby causing the inactivation of E2F. Skip1, Cullin, F-box complex. This E3 ubiquitin protein ligase plays various roles in the cell that are determined by the F-box protein identity. SIAMESE/SIAMESE-RELATED. This plant-specific class of CKIs that potentially targets both CDKA and CDKB responds strongly to a diverse set of environmental stimuli. Two members have been implicated in endocycle control as well. Epidermal hair on the shoot. The unicellular trichomes of Arabidopsis have a DNA content of 16C to 32C. Because of their accessibility for genetics and cell biology, trichomes have served as a model system for endoreplication studies. This tyrosine kinase that inactivates CDK through direct phosphorylation controls endocycle progression in tomato and maize, but not in Arabidopsis, where it rather involved in the DNA replication checkpoint.