资源环境科技发展态势分析平台

A key DNA-repair enzyme has a surprising role during the early steps in the assembly of ribosomes - the molecular machines that translate the genetic code into protein.

Charged pions(1) are the lightest and longest-lived mesons. Mesonic atoms are formed when an orbital electron in an atom is replaced by a negatively charged meson. Laser spectroscopy of these atoms should permit the mass and other properties of the meson to be determined with high precision and could place upper limits on exotic forces involving mesons (as has been done in other experiments on antiprotons(2-9)). Determining the mass of the pi(-) meson in particular could help to place direct experimental constraints on the mass of the muon antineutrino(10-13). However, laser excitations of mesonic atoms have not been previously achieved because of the small number of atoms that can be synthesized and their typically short (less than one picosecond) lifetimes against absorption of the mesons into the nuclei(1). Metastable pionic helium (pi He-4(+)) is a hypothetical(14-16) three-body atom composed of a helium-4 nucleus, an electron and a pi(-) occupying a Rydberg state of large principal (n approximate to 16) and orbital angular momentum (l approximate to n - 1) quantum numbers. The pi He-4(+) atom is predicted to have an anomalously long nanosecond-scale lifetime, which could allow laser spectroscopy to be carried out(17). Its atomic structure is unique owing to the absence of hyperfine interactions(18,19) between the spin-0 pi(-) and the He-4 nucleus. Here we synthesize pi He-4(+) in a superfluid-helium target and excite the transition (n, l) = (17, 16) -> (17, 15) of the pi(-)-occupied pi He-4(+) orbital at a near-infrared resonance frequency of 183,760 gigahertz. The laser initiates electromagnetic cascade processes that end with the nucleus absorbing the pi(-) and undergoing fission(20,21). The detection of emerging neutron, proton and deuteron fragments signals the laser-induced resonance in the atom, thereby confirming the presence of pi He-4(+). This work enables the use of the experimental techniques of quantum optics to study a meson.

Long-lived pionic helium atoms (composed of a helium-4 nucleus, an electron and a negatively charged pion) are synthesized in a superfluid-helium target, as confirmed by laser spectroscopy involving the pion-occupied orbitals.

Various species of the intestinal microbiota have been associated with the development of colorectal cancer(1,2), but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin(3). This compound is believed to alkylate DNA on adenine residues(4,5) and induces double-strand breaks in cultured cells(3). Here we expose human intestinal organoids to genotoxic pks(+)E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.

Organoids derived from human intestinal cells that are co-cultured with bacteria carrying the genotoxic pks(+) island develop a distinct mutational signature associated with colorectal cancer.

Transcription challenges the integrity of replicating chromosomes by generating topological stress and conflicts with forks(1,2). The DNA topoisomerases Top1 and Top2 and the HMGB family protein Hmo1 assist DNA replication and transcription(3-6). Here we describe the topological architecture of genes in Saccharomyces cerevisiae during the G1 and S phases of the cell cycle. We found under-wound DNA at gene boundaries and over-wound DNA within coding regions. This arrangement does not depend on Pol II or S phase. Top2 and Hmo1 preserve negative supercoil at gene boundaries, while Top1 acts at coding regions. Transcription generates RNA-DNA hybrids within coding regions, independently of fork orientation. During S phase, Hmo1 protects under-wound DNA from Top2, while Top2 confines Pol II and Top1 at coding units, counteracting transcription leakage and aberrant hybrids at gene boundaries. Negative supercoil at gene boundaries prevents supercoil diffusion and nucleosome repositioning at coding regions. DNA looping occurs at Top2 clusters. We propose that Hmo1 locks gene boundaries in a cruciform conformation and, with Top2, modulates the architecture of genes that retain the memory of the topological arrangements even when transcription is repressed.