Human CHD1 is required for early DNA-damage signaling and is uniquely regulated by its N terminus.

CHD1 is a conserved chromatin remodeling enzyme required for development and linked to prostate cancer in adults, yet its role in human cells is poorly understood. Here, we show that targeted disruption of the CHD1 gene in human cells leads to a defect in early double-strand break (DSB) repair via homologous recombination (HR), resulting in hypersensitivity to ionizing radiation as well as PARP and PTEN inhibition. CHD1 knockout cells show reduced H2AX phosphorylation (γH2AX) and foci formation as well as impairments in CtIP recruitment to the damaged sites. Chromatin immunoprecipitation following a single DSB shows that the reduced levels of γH2AX accumulation at DSBs in CHD1-KO cells are due to both a global reduction in H2AX incorporation and poor retention of H2AX at the DSBs. We also identified a unique N-terminal region of CHD1 that inhibits the DNA binding, ATPase, and chromatin assembly and remodeling activities of CHD1. CHD1 lacking the N terminus was more active in rescuing the defects in γH2AX formation and CtIP recruitment in CHD1-KO cells than full-length CHD1, suggesting the N terminus is a negative regulator in cells. Our data point to a role for CHD1 in the DSB repair process and identify a novel regulatory region of the protein.

Human CHD2 is a chromatin assembly ATPase regulated by its chromo- and DNA-binding domains.

Chromodomain helicase DNA-binding protein 2 (CHD2) is an ATPase and a member of the SNF2-like family of helicase-related enzymes. Although deletions of CHD2 have been linked to developmental defects in mice and epileptic disorders in humans, little is known about its biochemical and cellular activities. In this study, we investigate the ATP-dependent activity of CHD2 and show that CHD2 catalyzes the assembly of chromatin into periodic arrays. We also show that the N-terminal region of CHD2, which contains tandem chromodomains, serves an auto-inhibitory role in both the DNA-binding and ATPase activities of CHD2. While loss of the N-terminal region leads to enhanced chromatin-stimulated ATPase activity, the N-terminal region is required for ATP-dependent chromatin remodeling by CHD2. In contrast, the C-terminal region, which contains a putative DNA-binding domain, selectively senses double-stranded DNA of at least 40 base pairs in length and enhances the ATPase and chromatin remodeling activities of CHD2. Our study shows that the accessory domains of CHD2 play central roles in both regulating the ATPase domain and conferring selectivity to chromatin substrates.

Understanding the Internal Conversion Efficiency of BiVO4/SnO2 Photoanodes for Solar Water Splitting: An Experimental and Computational Analysis.

This work aims to understand the spin-coating growth process of BiVO4 photoanodes from a photon absorption and conversion perspective. BiVO4 layers with thicknesses ranging from 7 to 48 nm and the role of a thin (<5 nm) SnO2 hole-blocking layer have been studied. The internal absorbed photon-to-current efficiency (APCE) is found to be nonconstant, following a specific dependence of the internal charge separation and extraction on the increasing thickness. This APCE variation with BiVO4 thickness is key for precise computational simulation of light propagation in BiVO4 based on the transfer matrix method. Results are used for accurate incident photon-to-current efficiency (IPCE) prediction and will help in computational modeling of BiVO4 and other metal oxide photoanodes. This establishes a method to obtain the sample's thickness by knowing its IPCE, accounting for the change in the internal APCE conversion. Moreover, an improvement in fill factor and photogenerated voltage is attributed to the intermediate SnO2 hole-blocking layer, which was shown to have a negligible optical effect but to enhance charge separation and extraction for the lower energetic wavelengths. A Mott-Schottky analysis was used to confirm a photovoltage shift of 90 mV of the flat-band potential.