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The Mre11-Rad50-Nbs1 (MRN) complex recognizes and processes DNA double-strand breaks for homologous recombination by performing short-range removal of 5ʹ strands. Endonucleolytic processing by MRN requires a stably bound protein at the break site—a role we postulate is played by DNA-dependent protein kinase (DNA-PK) in mammals. Here we interrogate sites of MRN-dependent processing by identifying sites of CtIP association and by sequencing DNA-PK-bound DNA fragments that are products of MRN cleavage. These intermediates are generated most efficiently when DNA-PK is catalytically blocked, yielding products within 200 bp of the break site, whereas DNA-PK products in the absence of kinase inhibition show greater dispersal. Use of light-activated Cas9 to induce breaks facilitates temporal resolution of DNA-PK and Mre11 binding, showing that both complexes bind to DNA ends before release of DNA-PK-bound products. These results support a sequential model of double-strand break repair involving collaborative interactions between homologous and non-homologous repair complexes.

 

Convective parameterization is the long-lasting bottleneck of global climate modelling and one of the most difficult problems in atmospheric sciences. Uncertainty in convective parameterization is the leading cause of the widespread climate sensitivity in IPCC global warming projections. This paper reviews the observations and parameterizations of atmospheric convection with emphasis on the cloud structure, bulk effects, and closure assumption. The representative state-of-the-art convection schemes are presented, including the ECMWF convection scheme, the Grell scheme used in NCEP model and WRF model, the Zhang-MacFarlane scheme used in NCAR and DOE models, and parameterizations of shallow moist convection. The observed convection has self-suppression mechanisms caused by entrainment in convective updrafts, surface cold pool generated by unsaturated convective downdrafts, and warm and dry lower troposphere created by mesoscale downdrafts. The post-convection environment is often characterized by “diamond sounding” suggesting an over-stabilization rather than barely returning to neutral state. Then the pre-convection environment is characterized by slow moistening of lower troposphere triggered by surface moisture convergence and other mechanisms. The over-stabilization and slow moistening make the convection events episodic and decouple the middle/upper troposphere from the boundary layer, making the state-type quasi-equilibrium hypothesis invalid. Right now, unsaturated convective downdrafts and especially mesoscale downdrafts are missing in most convection schemes, while some schemes are using undiluted convective updrafts, all of which favour easily turned-on convection linked to double-ITCZ (inter-tropical convergence zone), overly weak MJO (Madden-Julian Oscillation) and precocious diurnal precipitation maximum. We propose a new strategy for convection scheme development using reanalysis-driven model experiments such as the assimilation runs in weather prediction centres and the decadal prediction runs in climate modelling centres, aided by satellite simulators evaluating key characteristics such as the lifecycle of convective cloud-top distribution and stratiform precipitation fraction.