Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.05.13.090589

Recombination proteins differently control the acquisition of homeologous DNA during Bacillus subtilis natural chromosomal transformation

Serrano, E.·RAMOS, C.·Alonso, J. C.·AYORA, S.
View original source ↗Export metadata ↓

Abstract

In naturally competent Bacillus subtilis cells the acquisition of closely related genes occurs via homology-directed chromosomal transformation (CT), and its frequency decreases log-linearly with increased sequence divergence (SD) up to 15%. Beyond this and up to 23% SD the interspecies boundary prevails, the CT frequency marginally decreases, and short (<10-nucleotides) segments are integrated via homology-facilitated micro-homologous integration. Both poorly known CT mechanisms are RecA-dependent. Here we identify the recombination proteins required for the acquisition of interspecies DNA. The absence of AddAB, RecF, RecO, RuvAB or RecU, crucial for repair-by-recombination, does not affect CT. However, inactivation of dprA, radA, recJ, recX or recD2 strongly interfered with CT. Interspecies CT was abolished beyond ~8% SD in {Delta}dprA, ~10% in {Delta}recJ, {Delta}radA, {Delta}recX and 14% in {Delta}recD2 cells. We propose that DprA, RecX, RadA/Sms, RecJ and RecD2 help RecA to unconstrain speciation and gene flow. These functions are ultimately responsible for generating genetic diversity and facilitate CT and gene acquisition from bacteria of the same genus.

Source connections

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Serrano, E., RAMOS, C., Alonso, J. C., AYORA, S.. 2020-05-13. Recombination proteins differently control the acquisition of homeologous DNA during Bacillus subtilis natural chromosomal transformation. https://doi.org/10.1101/2020.05.13.090589

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Prevalent Integration of both Xenotropic and Ecotropic Murine Leukemia Virus in the Human Genome of Xenografts

Humanized mouse models are widely used in medical research to represent human conditions (1, 2), but their fidelity could be compromised by mouse-originated infections. However, their susceptibility to mouse pathogens are rarely questioned (3). Here we screened 1,619 publicly available genomic sequencing runs from patient-derived xenograft (PDX) models for the integration of murine leukemia virus (MLV), a rodent retrovirus exists in the mouse genome as an endogenous retrovirus (4), within the human genome. We discovered substantial enrichment of human-MLV chimeric DNA in approximately 25% of them. Analyzing the human-MLV junctions, we found about 90% of them bearing the unmistakable hallmarks of retroviral integration, including the canonical MLV boundaries and the distinctive 4-bp target site duplications (5, 6). It was also assumed that mouse strains without the highly infectious Bxv1 provirus are safe from MLV contamination in xenografts (7, 8). However, we found many PDX models derived from Bxv1- strains, including the widely used NSG strain, are also contaminated by the supposedly rodent-specific ecotropic MLV (E-MLV). We further confirmed a complete E-MLV integrated into the human genome by both HiFi and sanger sequencing. Our discovery raises concerns that mouse-to-human retroviral transmission and integration is more common and less restrictive than previously appreciated. They support examination of MLV integration as a feature of humanized mouse models with implications on the fidelity of these models in recapitulating human cells and tissues. Our discovery also has underscored the importance of comprehensively inactivation of porcine endogenous retroviruses for the clinical application of xenotransplatation (9, 10).

microbiology↗
bioRxiv2026

Necroptosis is a targetable driver of severe coronavirus pathogenesis

Human-pathogenic coronaviruses differ dramatically in pathogenicity but the underlying mechanisms are incompletely understood. Here, we demonstrate that highly pathogenic coronaviruses trigger necroptosis in the infected cells and lung tissues, whereas necroptosis is not detected in cells infected by seasonal coronavirus. Mechanistically, highly pathogenic coronaviruses produce Z-RNA, activate ZBP1 and initiates necroptotic cell death signaling, triggering necroinflammation and lung injury. In contrast, seasonal coronaviruses produce little to no Z-RNA, and do not activate necroptosis. Importantly, small-molecule inhibition of necroptosis attenuates inflammatory cytokine expression and markedly ameliorates lung damage in mice infected with all three highly pathogenic coronaviruses, independent of virus clearance. Overall, our study identifies necroptosis as a dominant mediator of coronavirus pathogenesis, and positions necroptosis blockade as a new therapeutic target against severe coronavirus diseases.

microbiology↗
bioRxiv2026

POM121 regulates lentiviral nuclear import in a capsid-host factor-dependent manner

Lentiviruses such as human immunodeficiency virus 1 (HIV-1) access the nuclear lumen through the nuclear pore complex (NPC), a process coordinated by the interactions between the viral capsid and nucleoporins (NUPs). Here, using unbiased proteomic screens, we identified several capsid-associated NUPs, including POM121. Depletion of POM121 impaired HIV-1 infection in multiple cell lines and in primary CD4+ T cells, whereas equine infectious anaemia virus (EIAV) infection was enhanced, indicating that POM121 effect is virus-specific. A cytoplasmic carboxy-terminal fragment of POM121, containing its FG-rich region inhibited HIV-1 and a broader range of lentiviruses. Analysis of HIV-1 capsid mutants showed that physical interaction with POM121 does not predict functional dependence, as capsids retaining POM121 binding remained insensitive to its depletion. Strikingly, loss of cyclophilin A (CypA) completely abolished HIV-1 dependence on POM121, whereas depletion of CPSF6 produced only partial rescue, demonstrating that POM121 sensitivity is dictated by the broader network of capsid-host interactions. Finally, POM121 depletion impaired HIV-1 nuclear accumulation and selectively disrupted the nuclear import of other viral and cellular cargo. Together, these findings identify POM121 as a selective regulator of lentiviral nuclear entry whose functional contribution is determined by capsid and host-factor context.

microbiology↗