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Fan et al. show that replisome disassembly during S phase is required for efficient DNA replication by recycling essential replisome components between chromatin-bound and soluble compartments., After two converging DNA replication forks meet, active replisomes are disassembled and unloaded from chromatin. A key process in replisome disassembly is the unloading of CMG helicases (CDC45–MCM–GINS), which is initiated in Caenorhabditis elegans and Xenopus laevis by the E3 ubiquitin ligase CRL2LRR1. Here, we show that human cells lacking LRR1 fail to unload CMG helicases and accumulate increasing amounts of chromatin-bound replisome components as cells progress through S phase. Markedly, we demonstrate that the failure to disassemble replisomes reduces the rate of DNA replication increasingly throughout S phase by sequestering rate-limiting replisome components on chromatin and blocking their recycling. Continued binding of CMG helicases to chromatin during G2 phase blocks mitosis by activating an ATR-mediated G2/M checkpoint. Finally, we provide evidence that LRR1 is an essential gene for human cell division, suggesting that CRL2LRR1 enzyme activity is required for the proliferation of cancer cells and is thus a potential target for cancer therapy.

Host-restricted lineages of gut bacteria often include many closely related strains, but this fine-scale diversity is rarely investigated. The specialized gut symbiont Snodgrassella alvi has codiversified with honeybees (Apis mellifera) and bumblebees (Bombus) for millions of years. Snodgrassella alvi strains are nearly identical for 16S rRNA gene sequences but have distinct gene repertoires potentially affecting host biology and community interactions. We examined S. alvi strain diversity within and between hosts using deep sequencing both of a single-copy coding gene (minD) and of the V4 region of the 16S rRNA gene. We sampled workers from domestic and feral A. mellifera colonies and wild-caught Bombus representing 14 species. Conventional analyses of community profiles, based on the V4 region of the 16S rRNA gene, failed to expose most strain variation. In contrast, the minD analysis revealed extensive strain variation within and between host species and individuals. Snodgrassella alvi strain diversity is significantly higher in A. mellifera than in Bombus, supporting the hypothesis that colony founding by swarms of workers enables retention of more diversity than colony founding by a single queen. Most Bombus individuals (72%) are dominated by a single S. alvi strain, whereas most A. mellifera (86%) possess multiple strains. No S. alvi strains are shared between A. mellifera and Bombus, indicating some host specificity. Among Bombus-restricted strains, some are restricted to a single host species or subgenus, while others occur in multiple subgenera. Findings demonstrate that strains diversify both within and between host species and can be highly specific or relatively generalized in their host associations.

Antibiotic resistance adversely affects clinical and public health on a global scale. Using the opportunistic human pathogen Pseudomonas aeruginosa , we show that increasing the number density of bacteria, on agar containing aminoglycoside antibiotics, can non-monotonically impact the survival of antibiotic-resistant mutants. Notably, at high cell densities, mutant survival is inhibited. A wide range of bacterial species can inhibit antibiotic-resistant mutants. Inhibition results from the metabolic breakdown of amino acids, which results in alkaline by-products. The consequent increase in pH acts in conjunction with aminoglycosides to mediate inhibition. Our work raises the possibility that the manipulation of microbial population structure and nutrient environment in conjunction with existing antibiotics could provide therapeutic approaches to combat antibiotic resistance.