ArabidopsisRibonucleotide Reductases Are Critical for Cell Cycle Progression, DNA Damage Repair, and Plant Development

Ribonucleotide reductase (RNR), comprising two large (R1) and two small (R2) subunits, catalyzes a rate-limiting step in the production of deoxyribonucleotides needed for DNA replication and repair. Previous studies in yeast and mammals indicated that defective RNR often led to cell cycle arrest, growth retardation, and p53-dependent apoptosis, whereas abnormally increased RNR activities led to higher mutation rates. Because plants are constantly exposed to environmental mutagens and plant cells are totipotent, an understanding of RNR function in plants is important. We isolated and characterized mutations in all three R2 genes (TSO2, RNR2A, and RNR2B) in Arabidopsis thaliana. tso2 mutants had reduced deoxyribonucleoside triphosphate (dNTP) levels and exhibited developmental defects, including callus-like floral organs and fasciated shoot apical meristems. tso2 single and tso2 rnr2a double mutants were more sensitive to UV-C light, and tso2 rnr2a seedlings exhibited increased DNA damage, massive programmed cell death, and release of transcriptional gene silencing. Analyses of single and double r2 mutants demonstrated that a normal dNTP pool and RNR function are critical for the plant response to mutagens and proper plant development. The correlation between DNA damage accumulation and the subsequent occurrence of apoptotic nuclei in tso2 rnr2a double mutants suggests that perhaps plants, like animals, can initiate programmed cell death upon sensing DNA damage.