Biology subjects

KUMAR, R.

Publications and source records attributed to KUMAR, R..

5 recordsLinked to original sources

bioRxiv2026

Expression genome-wide association study and differential methylome profiling reveal upstream regulators of drought memory genes in Arabidopsis thaliana

Plants adapt to recurrent drought through transcriptional memory, yet the upstream regulators remain largely unknown. This study integrated expression genome-wide association study (eGWAS) across 115 Arabidopsis thaliana ecotypes with differential methylome profiling to identify these regulators. Focusing on the memory genes LKR, HIS1-3, and DREB1A, eGWAS identified signaling and epigenetic loci involved in ABA/JA responses and DNA methylation. Methylome profiling by whole-genome bisulfite sequencing of ecotypes contrasting in drought tolerance, as well as in superinduction of memory genes, revealed significantly greater methylation variation during the second drought (D2) than during the first (D1), highlighting the role of epigenetic reprogramming in memory maintenance. Functional validation using T-DNA mutants demonstrated specific modulation of the D2/D1 induction ratio without affecting initial drought responses. Mutants of LKR eGWAS-delineated genes AT1G56660, AT2G19120, AT4G16490, and DEG3, those of HIS1-3 eGWAS genes AT1G14220, AT2G24960, AT3G10845, AT3G19340, CNGC10, EMB2770, GRF7, and RPP2A, and DREB1A eGWAS genes AT1G67000, AT3G61610, AT5G62110, HK2, JMJ12, and LUP5 abolished respective memory gene induction. The eGWAS and methylome approaches converged on DNA repair, chromatin modification, vesicular transport, and proteostasis as core memory hubs. These findings reveal a genetic-epigenetic interplay that coordinates transcriptional memory, priming plants for rapid reactivation of stress pathways during recurrent drought.

plant biology↗

bioRxiv2025

Moss BRCA2 lacking canonical DNA binding domain promotes efficient homologous recombination and binds to DNA

BRCA2 interacts with RAD51 and DMC1 recombinases and binds to single-stranded DNA (ssDNA), through its canonical DNA binding domain (DBD) to mediate homology-directed DNA repair (HDR). While the well-folded DBD is widely conserved in diverse eukaryotes, a non-canonical BRCA2 variant lacking this domain is found in Drosophila melanogaster. Whether such a non-canonical BRCA2 variant exists in other species is unknown. Additionally, the DNA-binding activity of a BRCA2 variant lacking DBD remains unclear. Here, we identify a new non-canonical BRCA2 in the model plant Physcomitrium patens (PpBRCA2). We establish that PpBRCA2 is essential for genome integrity maintenance, somatic DNA repair, HDR-mediated gene targeting, and RAD51 foci recruitment at DNA break sites. PpBRCA2 is also critical for DNA repair during meiosis, but interacts only weakly with DMC1, suggesting a distinct meiotic function compared to other BRCA2 homologs. Despite lacking the canonical DBD, PpBRCA2 binds ssDNA through its disordered N-terminal region and efficiently promotes HDR. Our work highlights that the ssDNA binding capacity of BRCA2 homologs is conserved regardless of the presence of canonical DBD and provides a deeper understanding of BRCA2s functional diversity across species. Three Key messagesO_LIPhyscomitrium patens BRCA2 (PpBRCA2) lacking canonical DBD mediates homologous recombination and promotes genome stability C_LIO_LIPpBRCA2 differentially interact with RAD51 and DMC1 C_LIO_LIPpBRCA2 binds single-stranded DNA via its N-terminal to compensate for the loss of canonical DBD C_LI

genetics↗

bioRxiv2025

Non-canonical activation of PAR1 induces autophagy in mammalian breast cancer cells

Whether autophagy is a boon or a bane for the body does not have a straightforward answer, as its consequences are intricately tied to the pathophysiological context that triggers its activation. The intricate nature of the effects of autophagy on the body, compounded by its multifaceted regulation through various upstream signaling pathways, warrants a relatively highly deep and nuanced research. This study delves into the regulation of autophagy through noncanonical activation of protease-activated receptor 1 (PAR1) by hemagglutinin protease (HAP). Unlike the canonical activation of PAR1 by thrombin, which enhances cell proliferation via mechanistic target of rapamycin (mTOR) signaling, HAP-induced activation downregulates mTOR and triggers autophagy in mammalian breast cancer cells. This noncanonical activation generates an N-terminal sequence in PAR1, which, when mimicked by a synthetic peptide, induces autophagy independently of HAP. Further investigation in BALB/c mouse model of low-grade breast cancer reveals that the synthetic peptide-induced autophagy significantly inhibits tumor growth and delays carcinogenesis progression. Importantly, the lack of PAR1 expression in normal, healthy cells facilitates the peptide to selectively target cancerous cells with relatively high PAR1 expression, highlighting its potential as a therapeutic tool against low-grade breast cancer. These findings provide valuable insights into autophagy modulation via PAR1 and suggest a promising avenue for targeted cancer therapy.

cancer biology↗

bioRxiv2024

FIGL1 attenuates meiotic interhomolog repair and is counteracted by RAD51 paralog XRCC2 and chromosome axis protein ASY1 during meiosis

Two recombinases, RAD51 and DMC1, catalyze meiotic break repair to ensure crossovers (COs) between homologous chromosomes (interhomolog) rather than between sisters (intersister). FIDGETIN-LIKE-1 (FIGL1) downregulates both recombinases. However, the understanding of FIGL1 functions in meiotic repair remains limited. Here, we discover new genetic interactions of Arabidopsis thaliana FIGL1 that are important in vivo determinants of meiotic repair outcome. In figl1, compromising the RAD51-dependent repair by either losing RAD51 paralogs (RAD51B or XRCC2) or RAD54 or inhibiting RAD51s catalytic activity results in either unrepaired breaks or meiotic CO defects. Further, XRCC2 physically interacts with FIGL1 and partially counteracts FIGL1 for RAD51 focus formation. Our data support that RAD51-mediated repair mechanisms compensate for the FIGL1 dysfunction. FIGL1 is dispensable for intersister repair in dmc1 but is essential for meiotic repair completion in mutants with impaired DMC1 functions and interhomolog bias such as asy1. We show that FIGL1 attenuates interhomolog repair, and ASY1 counteracts FIGL1 to promote interhomolog recombination.

plant biology↗

bioRxiv2021

Effect of artificial light at night on sleep and metabolism in weaver birds

Artificial light at night is constantly minimizing the span of dark nights from the natural light-dark cycle of earth. Over the past century, the lightscape of earth has completely changed owing to technological advancements which subsequently changed the lifestyle of human as well as the nearby animal species. This motivated the present study, wherein we investigated the impact of light at night (LAN) on behavior and physiology of a diurnal passerine finch, baya weaver (Ploceus philippinus). A group of bird (N=10) exposed to 12L:12D photoperiod was initially subjected to dark nights (0 lux) for a period of 10 days followed by 5 lux; night light for a span of 4 weeks. First week in LAN served as acute treatment with respect to fourth week (chronic). Acute exposure had more pronounced impact on the behavioral and physiological observations when compared with chronic treatment. The results reveal significant increase in nighttime activity, sleep loss, significant inclusion of drowsiness behavior during the day in response to LAN. Beside these behavioral alterations, changes in physiological parameters such as; reduction in body mass, loss of gradient between pre- and post-prandial blood glucose levels, elevation in plasma corticosterone levels were more prominent during acute exposure of LAN. Plasma metabolites such as triglycerides, total protein, serum glutamic-oxaloacetic transaminase (SGOT) and creatinine concentrations also hiked in response to LAN treatment. Thus, the study broadly enumerates the impact of acute and chronic exposure of LAN on behavior (rest/sleep) and physiology (metabolism) of birds.

zoology↗