Oxygen (O2), a dominant element in the atmosphere and an essential molecule for most life on Earth, is produced by the photosynthetic oxidation of water. However, metabolic activity can cause the generation of reactive O2 species (ROS) that can damage lipids, proteins, nucleic acids, and threaten cell viability. To identify and characterize mechanisms that allow cells to cope with the potentially negative effects of O2 reactivity, we performed a high-throughput O2 sensitivity screen on a genome-wide insertional mutant library of the unicellular alga Chlamydomonas reinhardtii. This screen led to the identification of several genes that, when disrupted, alter the cell's sensitivity to O2 in the light. One of these genes encodes a protein designated Rubisco methyltransferase 2 (RMT2). Although this protein has homology to methyltransferases, it has not yet been demonstrated to catalyze methyltransferase reactions. Furthermore, the rmt2 mutant has not been observed to be compromised for the level of Rubisco (first enzyme of Calvin-Benson Cycle; CBC), although the mutant cells were light sensitive, which is reflected by a marked decrease in the level of photosystem I (PSI), with much less of an impact on the other photosynthetic complexes; this mutant also shows upregulation of genes encoding the Ycf3 and Ycf4 proteins, which are associated with the biogenesis of PSI. The RMT2 protein has a chloroplast targeting sequence predicted by PredAlgo and PB-Chlamy1,2, and rescue of the mutant with a wild-type (WT) copy of the gene fused to the mNeonGreen fluorophore indicates that the protein is within the chloroplast and appears to be enriched in/around the pyrenoid (an intrachloroplast compartment, potentially hypoxic, that is found in many algae that contain the CO2-fixing enzyme Rubisco), but we also observe it more dispersed throughout the stroma. These results suggest that RMT2 may serve an important role in the biogenesis of PSI and that PSI biogenesis may be enriched around or within the pyrenoid, which may reflect the impact of O2/reactive O2 species on the efficiency with which PSI can assemble.