Covalent organic frameworks (COFs) with well-defined and customizable pore structures are promising templates for the synthesis of nanomaterials with controllable sizes and dispersity. Herein, a thioether-containing COF has been rationally designed and used for the confined growth of ultrafine metal nanoparticles (NPs). Pt or Pd nanoparticles (Pt NPs and Pd NPs) immobilized inside the cavity of the COF material have been successfully prepared at a high loading with a narrow size distribution (1.7 ± 0.2 nm). We found the crystallinity of the COF support and the presence of thioether groups inside the cavities are critical for the size-controlled synthesis of ultrafine NPs. The as-prepared COF-supported ultrafine Pt NPs and Pd NPs show excellent catalytic activity respectively in nitrophenol reduction and Suzuki-Miyaura coupling reaction under mild conditions and low catalyst loading. More importantly, they are highly stable and easily recycled and reused without loss of their catalytic activities. Such COF-supported size-controlled synthesis of nanoparticles will open a new frontier on design and preparation of metal NP@COF composite materials for various potential applications, such as catalysis and development of optical and electronic materials.

A two-dimensional covalent organic monolayer was synthesized from simple aromatic triamine and dialdehyde building blocks by dynamic imine chemistry at the air/water interface (Langmuir-Blodgett method). The obtained monolayer was characterized by optical microscopy, scanning electron microscopy, and atomic force microscopy, which unambiguously confirmed the formation of a large (millimeter range), unimolecularly thin aromatic polyimine sheet. The imine-linked chemical structure of the obtained monolayer was characterized by tip-enhanced Raman spectroscopy, and the peak assignment was supported by spectra simulated by density functional theory. Given the modular nature and broad substrate scope of imine formation, the work reported herein opens up many new possibilities for the synthesis of customizable 2D polymers and systematic studies of their structure-property relationships.

CRISPR systems have emerged as transformative tools for altering genomes in living cells with unprecedented ease, inspiring keen interest in increasing their specificity for perfectly matched targets. We have developed a novel approach for improving specificity by incorporating chemical modifications in guide RNAs (gRNAs) at specific sites in their DNA recognition sequence (‘guide sequence’) and systematically evaluating their on-target and off-target activities in biochemical DNA cleavage assays and cell-based assays. Our results show that a chemical modification (2′-O-methyl-3′-phosphonoacetate, or ‘MP’) incorporated at select sites in the ribose-phosphate backbone of gRNAs can dramatically reduce off-target cleavage activities while maintaining high on-target performance, as demonstrated in clinically relevant genes. These findings reveal a unique method for enhancing specificity by chemically modifying the guide sequence in gRNAs. Our approach introduces a versatile tool for augmenting the performance of CRISPR systems for research, industrial and therapeutic applications.

We report a novel strategy for the controlled synthesis of gold nanoparticles (AuNPs) with narrow size distribution (1.9 ± 0.4 nm) through NP nucleation and growth inside the cavity of a well-defined three-dimensional, shape-persistent organic molecular cage. Our results show that both a well-defined cage structure and pendant thioether groups pointing inside the cavity are essential for the AuNP synthesis.

All cells rely on DNA polymerases to duplicate their genetic material and to repair or bypass DNA lesions. In humans, 16 polymerases have been identified, and each bears specific functions in genome maintenance. We identified here the recently discovered polymerase POLN to be involved in repair of DNA cross-links. Such DNA lesions are highly toxic and are believed to be repaired by the sequential activity of nucleotide excision repair, translesion synthesis, and homologous recombination mechanisms. By functionally assaying its role in these processes, we unraveled an unexpected involvement of POLN in homologous recombination. Moreover, we obtained evidence for physical and functional interaction of POLN with factors belonging to the Fanconi anemia pathway, a master regulator of cross-link repair. Finally, we show that POLN interacts and cooperates in DNA repair with the helicase HEL308, which shares a common origin with POLN in the Drosophila mus308 gene. Our data indicate that this novel polymerase-helicase complex participates in homologous recombination repair and is essential for cellular protection against DNA cross-links.Cells are continuously threatened by DNA damage that can potentially alter their genetic information. Numerous overlapping mechanisms exist to deal with DNA lesions. During S phase, unrepaired DNA lesions can block the progression of the replication machinery, causing cell cycle arrest and cell death. Cells have evolved mechanisms that signal the stalling of replication forks and recruit enzymes that can quickly restart these structures. Thus, replication forks can bypass the lesion without removing it. Homologous recombination (HR) and translesion synthesis (TLS) represent the most common mechanisms for dealing with stalled replication forks. In HR, the information on the newly replicated sister chromatid is used to overcome the lesion (32). In contrast, TLS uses special DNA polymerases that are able to replicate damaged DNA. Often, however, TLS polymerases insert wrong nucleotides across lesions, leading to mutations. Most polymerases involved in TLS belong to the Y family of DNA polymerases (2,7,29), which in addition to their characteristic catalytic domains and PCNA interaction protein (PIP) motifs, also have ubiquitinbinding domains toward their C termini. These domains are required for interaction with ubiquitinated PCNA and are essential for their recruitment to stalled replication forks. PCNA is an essential cofactor of DNA polymerases during replication, and it becomes monoubiquitinated when the replication fork is stalled at a damaged site (22). POLN (DNA polymerase ) is a recently discovered enzyme, belonging to the A family of DNA polymerases (16). In vitro, POLN is capable of DNA-templated synthesis, but it shows high mutagenicity, with a preference for inserting T across G and G across T (37). However, its lesion bypass activity is restricted to a subclass of DNA damage, namely, thymine glycol lesions (37). This suggests that POLN might not act as a TLS polymerase in vivo. S...