We used a proteomic approach to identify phosphopeptide-binding modules mediating signal transduction events in the DNA damage response pathway. Using a library of partially degenerate phosphopeptides, we identified tandem BRCT (BRCA1 carboxyl-terminal) domains in PTIP (Pax transactivation domain-interacting protein) and in BRCA1 as phosphoserine- or phosphothreonine-specific binding modules that recognize substrates phosphorylated by the kinases ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia- and RAD3-related) in response to gamma-irradiation. PTIP tandem BRCT domains are responsible for phosphorylation-dependent protein localization into 53BP1- and phospho-H2AX (gamma-H2AX)-containing nuclear foci, a marker of DNA damage. These findings provide a molecular basis for BRCT domain function in the DNA damage response and may help to explain why the BRCA1 BRCT domain mutation Met1775 --> Arg, which fails to bind phosphopeptides, predisposes women to breast and ovarian cancer.

The cellular response to DNA damage is mediated by evolutionarily conserved Ser/Thr kinases, phosphorylation of Cdc25 protein phosphatases, binding to 14-3-3 proteins, and exit from the cell cycle. To investigate DNA damage responses mediated by the p38/stress-activated protein kinase (SAPK) axis of signaling, the optimal phosphorylation motifs of mammalian p38alpha SAPK and MAPKAP kinase-2 were determined. The optimal substrate motif for MAPKAP kinase-2, but not for p38 SAPK, closely matches the 14-3-3 binding site on Cdc25B/C. We show that MAPKAP kinase-2 is directly responsible for Cdc25B/C phosphorylation and 14-3-3 binding in vitro and in response to UV-induced DNA damage within mammalian cells. Downregulation of MAPKAP kinase-2 eliminates DNA damage-induced G2/M, G1, and intra S phase checkpoints. We propose that MAPKAP kinase-2 is a new member of the DNA damage checkpoint kinase family that functions in parallel with Chk1 and Chk2 to integrate DNA damage signaling responses and cell cycle arrest in mammalian cells.

Phosphorylation of histone H3 is implicated in transcriptional activation and chromosome condensation, but its immediate molecular function has remained obscure. By affinity chromatography of nuclear extracts against modified H3 tail peptides, we identified 14-3-3 isoforms as proteins that bind these tails in a strictly phosphorylation-dependent manner. Acetylation of lysines 9 and 14 does not impede 14-3-3 binding to serine 10-phosphorylated H3 tails. In vivo, 14-3-3 is inducibly recruited to c-fos and c-jun nucleosomes upon gene activation, concomitant with H3 phosphoacetylation. We have determined the structures of 14-3-3zeta complexed with serine 10-phosphorylated or phosphoacetylated H3 peptides. These reveal a distinct mode of 14-3-3/phosphopeptide binding and provide a structural understanding for the lack of effect of acetylation at lysines 9 and 14 on this interaction. 14-3-3 isoforms thus represent a class of proteins that mediate the effect of histone phosphorylation at inducible genes.

We present an optimized 1992–2008 coupled ice‐ocean simulation of the Arctic Ocean. A Green's function approach adjusts a set of parameters for best model‐data agreement. Overall, model‐data differences are reduced by 45%. The optimized simulation reproduces the negative trends in ice extent in the satellite records. Volume and thickness distributions are comparable to those from the Ice, Cloud, and land Elevation Satellite (2003–2008). The upper cold halocline is consistent with observations in the western Arctic. The freshwater budget of the Arctic Ocean and volume/heat transports of Pacific and Atlantic waters across major passages are comparable with observation‐based estimates. We note that the optimized parameters depend on the selected atmospheric forcing. The use of the 25 year Japanese reanalysis results in sea ice albedos that are consistent with field observations. Simulated Pacific Water enters the Bering Strait and flows off the Chukchi Shelf along four distinct channels. This water takes ∼5–10 years to exit the Arctic Ocean at the Canadian Arctic Archipelago, Nares, or Fram straits. Atlantic Water entering the Fram Strait flows eastward, merges with the St Ana Trough inflow, and splits into two branches at the southwest corner of the Makarov Basin. One branch flows along Lomonosov Ridge back to Fram Strait. The other enters the western Arctic, circulates cyclonically below the halocline, and exits mainly through the Nares and Fram straits. This work utilizes the record of available observations to obtain an Arctic Ocean simulation that is in agreement with observations both within and beyond the optimization period and that can be used for tracer and process studies.

[1] The halocline in the Arctic Ocean plays an important role in regulating heat exchange at the bottom of the mixed layer and it has a direct effect on the ocean sea ice energy balance and sea ice mass balance. Modeling the halocline, however, remains a challenge in current state-of-the-art coupled ocean sea ice models including those that participated in the Arctic Ocean Model Intercomparison Project. In this study, we successfully reproduce a cold halocline in the Canada Basin by implementing a subgrid-scale brine rejection parameterization in an ocean general circulation model. The brine rejection scheme improves the solution by redistributing surface salts rejected during sea ice formation to their neutral buoyancy depths. The depths are based on salt plume physics and published laboratory and numerical experiments. Compared with hydrographic data from 1993 to 2004, distribution of most of the rejected salt to the bottom of the mixed layer seems to yield the lowest model-data misfits. We also show that the model's mixed layer depth is sensitive to the background diffusivity n used in the k-profile parameterization vertical mixing scheme. A background diffusivity of 10 À6 m 2 /s in combination with brine rejection scheme described herein yield the best simulation of the Arctic halocline.

[1] The Arctic freshwater (FW) has been the focus of many modeling studies, due to the potential impact of Arctic FW on the deep water formation in the North Atlantic. A comparison of the hindcasts from ten ocean-sea ice models shows that the simulation of the Arctic FW budget is quite different in the investigated models. While they agree on the general sink and source terms of the Arctic FW budget, the long-term means as well as the variability of the FW export vary among models. The best model-to-model agreement is found for the interannual and seasonal variability of the solid FW export and the solid FW storage, which also agree well with observations. For the interannual and seasonal variability of the liquid FW export, the agreement among models is better for the Canadian Arctic Archipelago (CAA) than for Fram Strait. The reason for this is that models are more consistent in simulating volume flux anomalies than salinity anomalies and volume-flux anomalies dominate the liquid FW export variability in the CAA but not in Fram Strait. The seasonal cycle of the liquid FW export generally shows a better agreement among models than the interannual variability, and compared to observations the models capture the seasonality of the liquid FW export rather well. In order to improve future simulations of the Arctic FW budget, the simulation of the salinity field needs to be improved, so that model results on the variability of the liquid FW export and storage become more robust.

[1] Six Arctic Ocean Model Intercomparison Project model simulations are compared with estimates of sea ice thickness derived from pan-Arctic satellite freeboard measurements (2004)(2005)(2006)(2007)(2008); airborne electromagnetic measurements (2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009); ice draft data from moored instruments in Fram Strait, the Greenland Sea, and the Beaufort Sea (1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008) and from submarines ; and drill hole data from the Arctic basin, Laptev, and East Siberian marginal seas (1982)(1983)(1984)(1985)(1986) and coastal stations (1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009). Despite an assessment of six models that differ in numerical methods, resolution, domain, forcing, and boundary conditions, the models generally overestimate the thickness of measured ice thinner than $2 m and underestimate the thickness of ice measured thicker than about $2 m. In the regions of flat immobile landfast ice (shallow Siberian Seas with depths less than 25-30 m), the models generally overestimate both the total observed sea ice thickness and rates of September and October ice growth from observations by more than 4 times and more than one standard deviation, respectively. The models do not reproduce conditions of fast ice formation and growth. Instead, the modeled fast ice is replaced with pack ice which drifts, generating ridges of increasing ice thickness, in addition to thermodynamic ice growth. Considering all observational data sets, the better correlations and smaller differences from observations are from the Estimating the Circulation and Climate of the Ocean, Phase II and Pan-Arctic Ice Ocean Modeling and Assimilation System models.

Abstract. A realistic representation of sea-ice deformation in models is important for accurate simulation of the sea-ice mass balance. Simulated sea-ice deformation from numerical simulations with 4.5, 9, and 18 km horizontal grid spacing and a viscous–plastic (VP) sea-ice rheology are compared with synthetic aperture radar (SAR) satellite observations (RGPS, RADARSAT Geophysical Processor System) for the time period 1996–2008. All three simulations can reproduce the large-scale ice deformation patterns, but small-scale sea-ice deformations and linear kinematic features (LKFs) are not adequately reproduced. The mean sea-ice total deformation rate is about 40 % lower in all model solutions than in the satellite observations, especially in the seasonal sea-ice zone. A decrease in model grid spacing, however, produces a higher density and more localized ice deformation features. The 4.5 km simulation produces some linear kinematic features, but not with the right frequency. The dependence on length scale and probability density functions (PDFs) of absolute divergence and shear for all three model solutions show a power-law scaling behavior similar to RGPS observations, contrary to what was found in some previous studies. Overall, the 4.5 km simulation produces the most realistic divergence, vorticity, and shear when compared with RGPS data. This study provides an evaluation of high and coarse-resolution viscous–plastic sea-ice simulations based on spatial distribution, time series, and power-law scaling metrics.