Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients’ smoking status, and the response to immunotherapy.
The bacterium Deinococcus radiodurans survives ionizing irradiation and other DNA-damaging assaults at doses that are lethal to all other organisms. How D. radiodurans accurately reconstructs its genome from hundreds of radiation-generated fragments in the absence of an intact template is unknown. Here we show that the D. radiodurans genome assumes an unusual toroidal morphology that may contribute to its radioresistance. We propose that, because of restricted diffusion within the tightly packed and laterally ordered DNA toroids, radiation-generated free DNA ends are held together, which may facilitate template-independent yet error-free joining of DNA breaks.
Exposing cells to folding stress causes a subset of their proteins to misfold and accumulate in inclusion bodies (IBs). IB formation and clearance are both active processes, but little is known about their mechanism. To shed light on this issue, we performed a screen with over 4,000 fluorescently tagged yeast proteins for co-localization with a model misfolded protein that marks IBs during folding stress. We identified 13 proteins that co-localize to IBs. Remarkably, one of these IB proteins, the uncharacterized and conserved protein Iml2, exhibited strong physical interactions with lipid droplet (LD) proteins. Indeed, we here show that IBs and LDs are spatially and functionally linked. We further demonstrate a mechanism for IB clearance via a sterol-based metabolite emanating from LDs. Our findings therefore uncover a function for Iml2 and LDs in regulating a critical stage of cellular proteostasis.
The inducible SOS response increases the ability of bacteria to cope with DNA damage through various DNA repair processes in which the RecA protein plays a central role. Here we present the first study of the morphological aspects that accompany the SOS response in Escherichia coli. We find that induction of the SOS system in wild-type bacteria results in a fast and massive intracellular coaggregation of RecA and DNA into a lateral macroscopic assembly. The coaggregates comprise substantial portions of both the cellular RecA and the DNA complement. The structural features of the coaggregates and their relation to in vitro RecA-DNA networks, as well as morphological studies of strains carrying RecA mutants, are all consistent with the possibility that the intracellular assemblies represent a functional entity in which RecA-mediated DNA repair and protection activities occur.biocrystallization ͉ DNA repair ͉ homology search ͉ stress response R ecA-mediated DNA recombination and repair processes proceed through several sequential phases (1-3). A presynaptic filament in which RecA molecules coat a single-stranded DNA substrate is initially formed. The filament acts then as a sequence-specific DNA-binding entity, capable of searching and binding dsDNA sites that are homologous to the RecA-coated segment. Within the resulting joint species, DNA strand exchange and heteroduplex extension processes are promoted. The mechanism that enables a rapid search for DNA homology in vivo, within a highly crowded and complex genome, remains enigmatic.To reach its target, any sequence-specific DNA-binding protein must overcome two general obstacles: a minute cellular concentration of the target, and a vast excess of nontarget, yet still competitive, DNA sites. The search for a homologous DNA site conducted by the RecA-DNA presynaptic filament shares these hurdles, but is further encumbered by the uniquely adverse diffusion characteristics of its components. A DNA target corresponds to a segment that is part of, and embedded within, the chromosome. This, and the large structural asymmetry of DNA, conspire to minimize the diffusion constant of DNA sites (4, 5). In a homology search executed by the RecA-DNA filament, both the searching and the target entities are chromosomal DNA sites whose small diffusion constants drastically attenuate their encounter rate. How then does a RecA-mediated intracellular search evade the kinetic impediments that are intrinsic to the nature of its components?Here we show that damages inflicted on bacterial DNA lead to a rapid formation of an ordered intracellular assembly that accommodates both RecA and DNA. We suggest that the striated morphology of this RecA-DNA assembly is capable of promoting an in vivo homology search by attenuating both the sampling volume and the dimensionality of the process. Moreover, RecA was shown to protect chromosomal DNA from degradation (6) through unknown mechanisms. The tight crystalline packaging that is progressively assumed by the intracellular RecA-DNA assemblies as ...
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