Biology subjects

Janas, T.

Publications and source records attributed to Janas, T..

3 recordsLinked to original sources

bioRxiv2026

Bacterial vitamin sharing emerges from a balance between release and uptake

Vitamin availability often shapes microbial communities, as many microbes use vitamins they cannot synthesize. Yet how vitamins become available to users remains poorly understood. To explore this process, we quantified vitamin B12 synthesis, uptake, and extracellular accumulation across hundreds of diverse soil, freshwater, and marine bacterial isolates. These measurements revealed distinct source-sink phenotypes and showed that producers vary substantially in the amount of B12 they provide extracellularly. B12 synthesis was predictable across divergent bacterial lineages from genome content, whereas uptake and extracellular accumulation were not. Controlled cell-death experiments and independently parameterized models showed that extracellular B12 could be quantitatively predicted from release by dead cells and reuptake by surviving cells. Thus, extracellular B12 availability is governed not by synthesis alone, but by the balance between release and uptake, with producer reuptake acting as a previously overlooked sink.

microbiology↗

bioRxiv2026

Stage-Specific Regulation of DNA Damage Repair by the Circadian Regulator, CRY1, in Prostate Cancer

Circadian dysregulation is increasingly linked to prostate cancer (PCa) progression, yet its role in directing DNA damage response (DDR) pathway selection remains poorly understood. Here, we identify circadian cryptochrome 1 (CRY1), a core circadian regulator, as a stage-specific determinant of DDR dependencies. Integrated transcriptomic and CRISPR-based analyses reveal that CRY1 promotes non-homologous end joining (NHEJ) and base excision repair (BER)-associated programs in hormone-sensitive disease (HTS), while driving a switch toward homologous recombination (HR) dependency in castration-resistant prostate cancer (CRPC). Mechanistically, CRY1 couples proliferative signaling to genome maintenance, enabling tumor cells to tolerate genotoxic stress and sustain progression. Notably, loss of CRY1 exposes distinct, context-dependent DDR vulnerabilities, revealing repair plasticity as a targetable actionable feature of disease evolution. These findings position CRY1 as a central regulator of DDR rewiring and support CRY1-directed combination strategies with DDR inhibitors as a rationale to delay or prevent progression to advanced, treatment-resistant PCa.

cancer biology↗

bioRxiv2024

AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer

Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease. CBP/p300 bromodomain inhibition enhances response to standard of care therapeutics. Functional studies, CBP/p300 cistrome mapping, and transcriptome in CRPC revealed that CBP/p300 regulates DDR. Further mechanistic investigation showed that CBP/p300 attenuation via therapeutic targeting and genomic knockdown decreases homologous recombination (HR) factors in vitro, in vivo, and in human prostate cancer (PCa) tumors ex vivo. Similarly, CBP/p300 expression in human prostate tissue correlates with HR factors. Lastly, targeting CBP/p300 impacts HR-mediate repair and patient outcome. Collectively, these studies identify CBP/p300 as drivers of PCa tumorigenesis and lay the groundwork to optimize therapeutic strategies for advanced PCa via CBP/p300 inhibition, potentially in combination with AR-directed and DDR therapies.

cancer biology↗