Biology subjects

Sonmez, C.

Publications and source records attributed to Sonmez, C..

4 recordsLinked to original sources

bioRxiv2025

The ERCC6L2-MRI-KU complex coordinates NHEJ at staggered DNA double-strand breaks.

ERCC6L2 disease is a recessive bone marrow failure (BMF) syndrome caused by mutations in the SNF2-like putative DNA helicase ERCC6L2. While implicated in DNA replication, double strand break (DSB) repair via non-homologous end joining (NHEJ), and interstrand crosslink (ICL) repair, how ERCC6L2 supports haematopoietic longevity remains unclear. Investigating this in vivo, we find that an Ercc6l2-deficient haematopoietic stem and progenitor cell (HSPC) compartment in mice is unexpectedly resilient. Ercc6l2 loss was also tolerated in mice co-deficient for endogenous formaldehyde detoxification, which precipitates early-onset BMF in models of Fanconi anaemia. Instead, Ercc6l2-deficient mice display a mild immunodeficiency, arising from defects in immunoglobulin class-switch recombination (CSR), that synergise with shieldin-deficiency, implicating ERCC6L2 and shieldin in distinct repair mechanisms. Furthermore, we demonstrate that ERRC6L2 stimulates chromosome fusions in the context of staggered, but not blunt dysfunctional telomeres. We reconcile ERCC6L2s NHEJ function through proteomic elucidation of its endogenous interactome and AlphaFold structural modelling to reveal a complex formed of ERCC6L2 and KU that is bridged by the NHEJ accessory factor MRI/CYREN. Consequently, ERCC6L2-MRI inter-dependence characterises CSR. Together, our findings implicate the ERCC6L2-MRI complex as a KU-regulatory DNA translocase coordinating classical-NHEJ at staggered-end DSBs. We suggest that similar staggered-end breaks represent the pathological substrates driving haematopoietic failure in ERCC6L2 disease.

molecular biology↗

bioRxiv2025

Sequential cold and heat stresses establish an intergenerational stress memory in rapeseed (Brassica napus L.)

Plants frequently experience temperature extremes that threaten growth and reproduction, yet their ability to retain and transmit stress responses across generations remains poorly understood. In this study, we investigated whether early cold exposure primes rapeseed seedlings for enhanced heat tolerance and whether such effects are inherited by the next generation. Seedlings were subjected to cold stress (4 {degrees}C for 3 weeks), heat stress (38 {degrees}C for 2 days), or sequential cold followed by heat stress. Control plants were grown under optimal conditions. We evaluated physiological, biochemical, and molecular traits in both the treated plants and their first-generation progeny. Temperature stress influenced flowering time, seed weight, seed oil content, and fatty acid composition. Genes involved in fatty acid metabolism, including BnaFAD2, BnaFAD5, BnaFATB, and BnaWD40, were differentially expressed. In the progeny of sequentially stressed plants, total phenolics, flavonoids, antioxidant activity, and chlorophyll content were significantly elevated, indicating the presence of intergenerational stress memory. Our findings show that sequential cold-heat stress not only enhances immediate stress tolerance but also induces heritable metabolic and physiological adaptations. These results provide new insights into the mechanisms of cross-tolerance and the potential for exploiting intergenerational stress memory in crop improvement.

plant biology↗

bioRxiv2024

Chromosome end protection by RAP1-mediated inhibition of DNA-PK

During classical non-homologous end joining (cNHEJ), DNA-dependent protein kinase (DNA-PK) encapsulates free DNA ends, forming a recruitment platform for downstream end-joining factors including Ligase 4 (LIG4)1. DNA-PK can also bind telomeres and regulate their resection2-4, but does not initiate cNHEJ at this position. How the end joining process is regulated in this context-specific manner is currently unclear. Here we show that the shelterin components TRF2 and RAP1 form a complex with DNA-PK that directly represses its end joining function at telomeres. Biochemical experiments and cryo-electron microscopy reveal that when bound to TRF2, RAP1 establishes a network of interactions with KU and DNA that prevents DNA-PK from recruiting LIG4. In mouse and human cells, RAP1 is redundant with the Apollo nuclease in repressing cNHEJ at chromosome ends, demonstrating that the inhibition of DNA-PK prevents telomere fusions in parallel with overhang-dependent mechanisms. Our experiments show that the end joining function of DNA-PK is directly and specifically repressed at telomeres, establishing a molecular mechanism for how individual linear chromosomes are maintained in mammalian cells.

biochemistry↗

bioRxiv2024

Unveiling the Impact of Vernalization on Seed Oil Content and Fatty Acid Composition in Rapeseed Through Simulated Shorter Winters

Climate change is leading to warmer winters world-wide with an increasing number of extreme events every year. Plants are majorly impacted by the escalating effects of global warming. In this study, we set up an experimental model to simulate warmer and shorter winters under laboratory conditions. Winter and spring varieties of rapeseed (Brassica napus L.) were subjected to diverse vernalization scenarios including three and four weeks-long vernalization as well as vernalization interruptions by one week-long devernalization at warm temperatures. The aim of the study was to assess the effects of the vernalization models on BnaFLC (BnaFLCA02, BnaFLCA10 and BnaFLCC02) expression, some yield related traits, a set of genes involved in fatty acid synthesis and seed oil content and fatty acid composition. A notable difference in vernalization responsiveness was observed in BnaFLCA02, BnaFLCA10, and BnaFLCC02 between the late-flowering winter variety, Darmor, the early-flowering winter variety Bristol and the spring variety, Helios, after a three-week vernalization period. Our findings unveil a robust correlation between vernalization and seed oil content, as well as fatty acid composition in rapeseed. While the expression levels of fatty acid synthesis-related genes, including BnaFAD2, BnaFAD5, BnaFATB, BnaMCOA (AAE13), and BnaWD40, exhibited significant changes under cold conditions in leaves, the expression levels of the same genes in developing seeds did not exhibit a strong correlation with vernalization, flowering time, or oil and fatty acid contents in seeds. Our results suggest that vernalization plays a role in seed oil biosynthesis beyond its impact on flowering time.

plant biology↗