Abstract
All eukaryotic cells replicate their nuclear DNA in a conserved manner, whereby the parent molecule is unwound and each DNA strand becomes the template for nascent DNA synthesis. Here we show that in in silico analysis for genes coexpressed with DNA replication genes, COEXPRESSED WITH DNA REPLICATION 1 (CDR1) gene was identified as a novel cell cycle regulator. CDR1 gene is highly coexpressed with DNA replication genes such as PCNAs, MCMs, DNA primase, and ETG1. Plants lacking the CDR1 gene had large leaves due to increase of cell number, but not endoreduplication, indicating that CDR1 arrests mitotic cell cycle progression. CDR1 encodes SINA E3 ligase protein that has been mainly associated with ubiquitin-dependent proteolysis. CDR1 gene is strongly expressed in dividing tissues such as shoot apex and root meristems. This expression is controlled by E2F transcription factors, as shown by upregulation in E2Fa/DPa overexpressing plants and the presence of E2F binding cis-element in the CDR1 promoter. Based on mutant characterization and gene structure, we postulate that CDR1 mediates cell cycle regulation through the degradation of cell cycle regulators.