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Base editors (BEs) are genome editing agents that install point mutations with high efficiency and specificity. Due to their reliance on uracil and inosine DNA damage intermediates (rather than double-strand DNA breaks, or DSBs), it has been hypothesized that BEs rely on more ubiquitous DNA repair pathways than DSB-reliant genome editing methods, which require processes that are only active during certain phases of the cell cycle. We report here the first systematic study of the cell cycle-dependence of base editing using cell synchronization experiments. We find that nickase-derived BEs (which introduce DNA backbone nicks opposite the uracil or inosine base) function independently of the cell cycle, while non-nicking BEs are highly dependent on S-phase (DNA synthesis phase). We found that synchronization in G1 (growth phase) during the process of cytosine base editing causes significant increases in C•G to A•T “byproduct” introduction rates, which can be leveraged to discover new strategies for precise C•G to A•T base editing. We observe that endogenous expression levels of DNA damage repair pathways are sufficient to process base editing intermediates into desired editing outcomes, and the process of base editing does not significantly perturb transcription levels. Overall, our study provides mechanistic data demonstrating the robustness of nickase-derived BEs for performing genome editing across the cell cycle. 

Abstract A subseasonal-to-seasonal (S2S) prediction system was recently developed using the GFDL Seamless System for Prediction and Earth System Research (SPEAR) global coupled model. Based on 20-yr hindcast results (2000–19), the boreal wintertime (November–April) Madden–Julian oscillation (MJO) prediction skill is revealed to reach 30 days measured before the anomaly correlation coefficient of the real-time multivariate (RMM) index drops to 0.5. However, when the MJO is partitioned into four distinct propagation patterns, the prediction range extends to 38, 31, and 31 days for the fast-propagating, slow-propagating, and jumping MJO patterns, respectively, but falls to 23 days for the standing MJO. A further improvement of MJO prediction requires attention to the standing MJO given its large gap with its potential predictability (38 days). The slow-propagating MJO detours southward when traversing the Maritime Continent (MC), and confronts the MC prediction barrier in the model, while the fast-propagating MJO moves across the central MC without this prediction barrier. The MJO diversity is modulated by stratospheric quasi-biennial oscillation (QBO): the standing (slow-propagating) MJO coincides with significant westerly (easterly) phases of QBO, partially explaining the contrasting MJO prediction skill between these two QBO phases. The SPEAR model shows its capability, beyond the propagation, in predicting their initiation for different types of MJO along with discrete precursory convection anomalies. The SPEAR model skillfully predicts the observed distinct teleconnections over the North Pacific and North America related to the standing, jumping, and fast-propagating MJO, but not the slow-propagating MJO. These findings highlight the complexities and challenges of incorporating MJO prediction into the operational prediction of meteorological variables. 

Abstract Compared to the Arctic, seasonal predictions of Antarctic sea ice have received relatively little attention. In this work, we utilize three coupled dynamical prediction systems developed at the Geophysical Fluid Dynamics Laboratory to assess the seasonal prediction skill and predictability of Antarctic sea ice. These systems, based on the FLOR, SPEAR_LO, and SPEAR_MED dynamical models, differ in their coupled model components, initialization techniques, atmospheric resolution, and model biases. Using suites of retrospective initialized seasonal predictions spanning 1992–2018, we investigate the role of these factors in determining Antarctic sea ice prediction skill and examine the mechanisms of regional sea ice predictability. We find that each system is capable of skillfully predicting regional Antarctic sea ice extent (SIE) with skill that exceeds a persistence forecast. Winter SIE is skillfully predicted 11 months in advance in the Weddell, Amundsen and Bellingshausen, Indian, and West Pacific sectors, whereas winter skill is notably lower in the Ross sector. Zonally advected upper ocean heat content anomalies are found to provide the crucial source of prediction skill for the winter sea ice edge position. The recently-developed SPEAR systems are more skillful than FLOR for summer sea ice predictions, owing to improvements in sea ice concentration and sea ice thickness initialization. Summer Weddell SIE is skillfully predicted up to 9 months in advance in SPEAR_MED, due to the persistence and drift of initialized sea ice thickness anomalies from the previous winter. Overall, these results suggest a promising potential for providing operational Antarctic sea ice predictions on seasonal timescales. 

We document the configuration and emergent simulation features from the Geophysical Fluid Dynamics Laboratory (GFDL) OM4.0 ocean/sea ice model. OM4 serves as the ocean/sea ice component for the GFDL climate and Earth system models. It is also used for climate science research and is contributing to the Coupled Model Intercomparison Project version 6 Ocean Model Intercomparison Project. The ocean component of OM4 uses version 6 of the Modular Ocean Model and the sea ice component uses version 2 of the Sea Ice Simulator, which have identical horizontal grid layouts (Arakawa C‐grid). We follow the Coordinated Ocean‐sea ice Reference Experiments protocol to assess simulation quality across a broad suite of climate‐relevant features. We present results from two versions differing by horizontal grid spacing and physical parameterizations: OM4p5 has nominal 0.5° spacing and includes mesoscale eddy parameterizations and OM4p25 has nominal 0.25° spacing with no mesoscale eddy parameterization. Modular Ocean Model version 6 makes use of a vertical Lagrangian‐remap algorithm that enables general vertical coordinates. We show that use of a hybrid depth‐isopycnal coordinate reduces the middepth ocean warming drift commonly found in purez^*vertical coordinate ocean models. To test the need for the mesoscale eddy parameterization used in OM4p5, we examine the results from a simulation that removes the eddy parameterization. The water mass structure and model drift are physically degraded relative to OM4p5, thus supporting the key role for a mesoscale closure at this resolution.