Biology subjects

Coego, A.

Publications and source records attributed to Coego, A..

3 recordsLinked to original sources

bioRxiv2026

The Holliday junction resolvase GEN1 preserves genome integrity and self-renewal in mouse embryonic stem cells

The maintenance of pluripotent stem cells (PSCs) under rapid proliferation requires mechanisms that both suppress replication-driven genome instability and preserve self-renewal capacity. Here, we show that, in contrast to somatic cells where it mainly acts as a backup, the Holliday junction resolvase GEN1 is required in mouse embryonic stem cells (ESCs), where its depletion severely compromises self-renewal and long-term maintenance. Loss of GEN1 induces the accumulation of cells with DNA content greater than 4C and chromosome fusions. Notably, a catalytically inactive GEN1 mutant rescues ESC colony formation, indicating that GEN1 supports ESC maintenance through non-enzymatic functions. In addition, GEN1 depletion increases ESC tolerance to topoisomerase I-mediated replication stress and renders this phenotype dependent on DNA-PK activity, suggesting that GEN1 loss alters how pluripotent cells cope with replication-associated DNA lesions. Together, these findings identify GEN1 as a non-redundant guardian of genome integrity in pluripotent cells, revealing both a catalysis-independent role in self-renewal and a contribution to the replication stress response, with implications for PSC genomic quality control. HighlightsO_LIIn contrast to somatic cells, GEN1 is specifically required for mouse pluripotent cell self-renewal and expansion in vitro. C_LIO_LIGEN1 loss induces accumulation of DNA content greater than 4C and chromosome fusions without loss of core pluripotency markers expression. C_LIO_LICatalytically inactive GEN1 mutant rescues ESC colony-forming capacity. C_LIO_LIGEN1 depletion increases ESC tolerance to topoisomerase I-mediated replication stress in a DNA-PK-dependent manner C_LI eTOCRamos-Lage et al. demonstrate that the resolvase GEN1 is essential for mouse embryonic stem cell self-renewal and genome stability. Strikingly, a catalytically dead mutant rescues colony formation, revealing an unexpected non-enzymatic role for GEN1 in pluripotency maintenance.

cell biology↗

bioRxiv2021

CAR modulates plasma membrane nano-organization and immune signaling downstream of RALF1-FERONIA ligand-receptor signaling system

O_LIThe receptor-like kinase (RLK) FERONIA (FER) senses peptide ligands in the plasma membrane (PM), modulates plant growth and development, and integrates biotic and abiotic stress signaling for downstream adaptive response. However, the molecular interplay of these diverse processes is largely unknown. C_LIO_LIHere, we show that FER, the receptor of Rapid Alkalinization Factor 1 (RALF1), physically interacts with C2 domain ABA-related (CAR) proteins to control the nano-organization of the PM in Arabidopsis. C_LIO_LIDuring this process, the RALF1-FER pathway upregulates CAR protein translation, and then more CAR proteins are recruited to PM. This acts as a rapid feedforward loop to stabilize PM liquid-ordered phase. FER interacts with and phosphorylates CARs, and reducing their lipid-binding ability, which breaks the feedback regulation CAR activity at latter time point. C_LIO_LISimilar to FER mutant, pentuple car14569 mutants inhibit flg22-induced FLS2-BAK1 immune complex formation, which depends on the integrity of nanodomains. O_LITogether, we propose that the FER-CAR module controls the formation of the PM nano-organization during RALF signaling through a self-contained amplifying loop including both positive and negative feedbacks. C_LI C_LI

plant biology↗

bioRxiv2020

PYL8 ABA receptors of Phoenix dactylifera play a crucial role in response to abiotic stress and are stabilized by ABA

The identification of those prevailing ABA receptors and molecular mechanisms that trigger drought adaptation in crops well adapted to harsh conditions such as date palm (Phoenix dactylifera, Pd) sheds light on plant-environment interactions. We reveal that PdPYL8-like receptors are predominantly expressed under abiotic stress, being Pd27 the most expressed receptor in date palm. Therefore, subfamily I PdPYL8-like receptors have been selected for ABA signaling during abiotic stress response in this crop. Biochemical characterization of PdPYL8-like and PdPYL1-like receptors revealed receptor- and ABA-dependent inhibition of PP2Cs, which triggers activation of the pRD29B-LUC reporter in response to ABA. PdPYLs efficiently abolish PP2C-mediated repression of ABA signaling, but loss of the Trp lock in the seed-specific AHG1-like phosphatase PdPP2C79 markedly impairs its inhibition by ABA receptors. Characterization of Arabidopsis transgenic plants that express PdPYLs shows enhanced ABA signaling in seed, root and guard cells. Specifically, Pd27 overexpressing (OE) plants showed lower ABA content and were more efficient than wild type to lower transpiration at negative soil water potential, leading to enhanced drought tolerance. Finally, PdPYL8-like receptors accumulate after ABA treatment, which suggests that ABA-induced stabilization of these receptors operates in date palm for efficient boosting of ABA signaling in response to abiotic stress. HighlightDate palm response to abiotic stress is triggered through PYL8-like ABA receptors that are stabilized by the hormone, which boosts plant adaptation to drought mediated by ABA.

plant biology↗