The plant cell cycle: Pre-Replication complex formation and controls

Abstract

The multiplication of cells in all living organisms requires a tight regulation of DNA replication. Several mechanisms take place to ensure that the DNA is replicated faithfully and just once per cell cycle in order to originate through mitoses two new daughter cells that contain exactly the same information from the previous one. A key control mechanism that occurs before cells enter S phase is the formation of a pre-replication complex (pre-RC) that is assembled at replication origins by the sequential association of the origin recognition complex, followed by Cdt1, Cdc6 and finally MCMs, licensing DNA to start replication. The identification of pre-RC members in all animal and plant species shows that this complex is conserved in eukaryotes and, more importantly, the differences between kingdoms might reflect their divergence in strategies on cell cycle regulation, as it must be integrated and adapted to the niche, ecosystem, and the organism peculiarities. Here, we provide an overview of the knowledge generated so far on the formation and the developmental controls of the pre-RC mechanism in plants, analyzing some particular aspects in comparison to other eukaryotes.

Figure 1. Overview of cell cycle control modulation at meristems by endogenous and exogenous signals. Plants are continuously sensing the environment and modulating their development by adjusting cell division and differentiation rates at the different meristems. This means that every plant meristem might be sensing exogenous signals and integrating with genetic controls, which leads to changes in gene expression that will finally balance cell proliferation and differentiation rates, culminating with the correct plant form. The shoot apical meristem (SAM) is represented in the right panel. An important control of the G1 to S transition of the cycle is the pre-replication complex (pre-RC) that might be continuously regulated, although by some different mechanisms, along development.

Figure 2. Hypothetical model of pre-RC formation and regulation in plants. (A) Pre-replication complex (Pre-RC) assembly, activation and prevention of DNA re-replication is regulated by three major levels of controls that act in a coordinated way, connecting cell cycle progression with endogenous and exogenous (environmental) signaling. Protein phosphorylation by CDK/cyclin regulates different steps of DNA replication licensing: (B) first, they phosphorylate retinoblastoma protein, releasing E2F/DP to (D) activate transcription of pre-RC genes; (C) later, phosphorylation of members of the pre-RC promotes initiation of DNA replication and prevents DNA re-replication through nuclear exclusion and/or protein degradation. In addition to the transcriptional regulation by E2F/DP (D), pre-RC assembly is limited by repression of CDT1 transcription (E) by ABAP1/TCP24 (F), which also interacts directly with CDT1. (G) GEM also competes for binding to CDT1 making it less available for pre-RC loading.