Decrotonylation of cGAS K254 prompts homologous recombination repair by blocking its DNA binding and releasing PARP1.

Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, also exhibits nuclear genomic localization and is involved in DNA damage signaling. In this study, we investigated the impact of cGAS crotonylation on the regulation of the DNA damage response, particularly homologous recombination repair, following exposure to ionizing radiation (IR). Lysine 254 of cGAS is constitutively crotonylated by the CREB-binding protein; however, IR-induced DNA damage triggers sirtuin 3 (SIRT3)-mediated decrotonylation. Lysine 254 decrotonylation decreased the DNA-binding affinity of cGAS and inhibited its interaction with PARP1, promoting homologous recombination repair. Moreover, SIRT3 suppression led to homologous recombination repair inhibition and markedly sensitized cancer cells to IR and DNA-damaging chemicals, highlighting SIRT3 as a potential target for cancer therapy. Overall, this study revealed the crucial role of cGAS crotonylation in the DNA damage response. Furthermore, we propose that modulating cGAS and SIRT3 activities could be potential strategies for cancer therapy.

RNA N6-Methyladenosine Modification in DNA Damage Response and Cancer Radiotherapy.

The N6-methyladenosine (M6A) modification is the most common internal chemical modification of RNA molecules in eukaryotes. This modification can affect mRNA metabolism, regulate RNA transcription, nuclear export, splicing, degradation, and translation, and significantly impact various aspects of physiology and pathobiology. Radiotherapy is the most common method of tumor treatment. Different intrinsic cellular mechanisms affect the response of cells to ionizing radiation (IR) and the effectiveness of cancer radiotherapy. In this review, we summarize and discuss recent advances in understanding the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage and in determining the outcomes of cancer radiotherapy. Insights into RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy and radioprotection of normal tissues.

Modular Synthesis of Biphen[n]arenes Directed by Five-Membered Heterocycles.

Modular synthesis of novel biphen[n]arenes (n = 2-4) with customizable heterocycle blocks, functional skeletons, binding sites, and topological structures could be facilely achieved through the rational design and replacement of reaction modules (furan and thiophene), functional modules (substituted benzene, biphenyl, and naphthalene), and linking modules (methylene). These biphen[n]arenes were characterized by NMR, HRMS, and X-ray crystalline diffraction, complemented by DFT calculations. Their photophysical properties were thoroughly studied.

Diverse applications and development of aptamer detection technology.

Aptamers have received extensive attention in recent years because of their advantages of high specificity, high sensitivity and low immunogenicity. Aptamers can perform almost all functions of antibodies through the combination of spatial structure and target, which are called "chemical antibodies". At present, aptamers have been widely used in cell imaging, new drug development, disease treatment, microbial detection and other fields. Due to the diversity of modifications, aptamers can be combined with different detection technologies to construct aptasensors. This review focuses on the diversity of aptamers in the field of detection and the development of aptamer-based detection technology and proposes new challenges for aptamers in this field.

Modular Introduction of endo-Binding Sites in a Macrocyclic Cavity towards Selective Recognition of Neutral Azacycles.

Macrocycles with a functionalized interior, which is a general cavity feature of bioreceptors, are relatively hard to synthesize. Here we report a modular strategy to customize diverse endo-binding sites in the macrocycle cavity. Only two steps are needed. First, one V-shaped functional module bearing an embedded binding site and two 2,5-dimethoxyphenyls as reaction modules are connected. Then the condensation of the resulting monomer and paraformaldehyde directly produces the designed macrocycle. V-shaped monomers are deliberately used to guarantee the binding sites equatorially directing inward into the cavity and 2,5-dimethoxyphenyls standing axially as macrocycle sidewalls. More than a dozen endo-functionalized macrocyclic receptors have been constructed. Host-guest complexation studies show that macrocycle BP1-decorated interior OH moieties can strongly encapsulate neutral azacycles by forming inner hydrogen bonds, giving a high association constant of 4.59×104  M-1 in non-polar media.