Repository Collection:

COSA-1-SLX-4 interaction directly links crossover designation with Holliday junction resolution

2026-03-31T15:00:00Z

Title: COSA-1-SLX-4 interaction directly links crossover designation with Holliday junction resolution Author(s): Liu, Guoteng; Yang, Yuejun; Nan, Wencong; Xiao, Tongxin; Guo, Zongyu; Zhang, Meiyu; Wang, Yuchen; Wu, Xuezhen; Gartner, Anton; Zhang, Hongtao; Hong, Ye Abstract: Crossover (CO) formation between homologous chromosomes is essential for genetic diversity and accurate meiotic chromosome segregation. This process involves two key steps: the designation of a subset of meiotic double-strand breaks to CO-designated sites and subsequent CO resolution by Holliday junction (HJ) resolvase. However, how these steps are functionally coupled remains elusive. Here, we showed that COSA-1, essential for CO designation, directly interacts with the SLX-4 scaffold protein, which organizes the SLX-1, XPF-1, and MUS-81 HJ resolvases. Disrupting this interaction results in persistent unrepaired recombination intermediates and defective CO formation. Notably, these defects can be largely rescued by the artificial tethering of SLX-4 to the CO designation proteins. We further demonstrate that COSA-1 promotes assembly of the SLX-4 resolvase complex and provide evidence that this mechanism coupling CO designation with resolution is evolutionarily conserved. Together, our findings support a model in which CO designation proteins ensure accurate CO formation by directly recruiting the resolution machinery.

Mapping isoforms and regulatory mechanisms from spatial transcriptomics data with SPLISOSM

2025-12-31T15:00:00Z

Title: Mapping isoforms and regulatory mechanisms from spatial transcriptomics data with SPLISOSM Author(s): Su, Jiayu; Qu, Yiming; Schertzer, Megan; Yang, Haochen; Jiang, Jiahao; Lhakhang, Tenzin; Nelson, Theodore M.; Park, Stella; Lai, Qiliang; Fu, Xi; Choi, Seung-won; Knowles, David A.; Rabadan, Raul Abstract: Transcript diversity including splicing and alternative 3 ' end usage is crucial for cellular identity and adaptation, yet its spatial coordination remains poorly understood. Here we present SPLISOSM (spatial isoform statistical modeling), a method for detecting isoform-resolution patterns from spatial transcriptomics data. SPLISOSM uses multivariate testing with nonparametric kernels to account for spot-level and isoform-level dependencies, achieving high statistical power on sparse data. In the mouse brain, we identify over 1,000 spatially variable transcript diversity events, primarily in synaptic signaling pathways linked to neuropsychiatric disorders, and uncover both known and previously unknown regulatory relationships with region-specific RNA binding proteins. We further show that these patterns are evolutionarily conserved between mouse and human prefrontal cortex. Analysis of human glioblastoma highlights pervasive transcript diversity in antigen presentation and adhesion genes associated with specific microenvironmental conditions. Together, we present a comprehensive spatial splicing analysis in the brain under normal and neoplastic conditions.

SMC-5/6 complex subunit NSE-1 plays a crucial role in meiosis and DNA repair in Caenorhabditis elegans

2024-04-30T15:00:00Z

Title: SMC-5/6 complex subunit NSE-1 plays a crucial role in meiosis and DNA repair in Caenorhabditis elegans Author(s): Odiba, Arome Solomon; Ezechukwu, Chiemekam Samuel; Liao, Guiyan; Hong, Ye; Fang, Wenxia; Jin, Cheng; Gartner, Anton; Wang, Bin Abstract: The SMC5/6 complex is evolutionarily conserved across all eukaryotes and plays a pivotal role in preserving genomic stability. Mutations in genes encoding SMC5/6 complex subunits have been associated with human lung disease, immunodeficiency, and chromosome breakage syndrome. Despite its critical importance, much about the SMC5/6 complex remains to be elucidated. Various evidences have suggested possible role of a subunit of the SMC5/6 complex, NSE1, in chromosome segregation and DNA repair. Current knowledge regarding the role of NSE1 is primarily derived from single-cell-based analyses in yeasts, Arabidopsis thaliana, and human cell lines. However, our understanding of its function is still limited and requires further investigation. This study delves into the role of nse-1 in Caenorhabditis elegans, revealing its involvement in meiotic recombination and DNA repair. nse-1 mutants display reduced fertility, increased male incidence, and increased sensitivity to genotoxic chemicals due to defects in meiotic chromosome segregation and DNA repair. These defects manifest as increased accumulation of RAD-51 foci, increased chromosome fragmentation, and susceptibility to MMS, cisplatin, and HU. Furthermore, nse-1 mutation exacerbates germ cell death by upregulating ced-13 and egl-1 genes involved in the CEP-1/p53-mediated apoptotic pathway. NSE-1 is essential for the proper localization of NSE-4 and MAGE-1 on the chromosomes. Collectively, these findings firmly establish nse-1 as a crucial factor in maintaining genomic stability.

Longitudinal trajectory of menopausal symptoms in premenopausal women throughout adjuvant chemotherapy: a two-stage analytical approach

2025-09-30T15:00:00Z

Title: Longitudinal trajectory of menopausal symptoms in premenopausal women throughout adjuvant chemotherapy: a two-stage analytical approach Author(s): Jung, Saim; Kim, Jaehyun; Lee, Sun Hyung; Shin, Joon Sung; Kim, Won-Hyoung; Jung, Dooyoung; Kim, Tae-Yong; Im, Seock-Ah; Lee, Kyung-Hun; Hahm, Bong-Jin; Yeom, Chan-Woo Abstract: Purpose Breast cancer incidence in Asian women peaks in the mid-40 s, when many remain premenopausal. The progression of chemotherapy-induced menopausal symptoms in this population remains underexplored. This study examined their temporal trajectory and clinical significance during adjuvant chemotherapy. Method This prospective study assessed breast cancer patients undergoing adjuvant chemotherapy at a tertiary hospital. Participants were classified by menopausal status and treated with AC-D (Adriamycin, Cyclophosphamide, and Docetaxel) or FAC (5-Fluorouracil, Adriamycin, and Cyclophosphamide) regimens. Menopausal symptoms were evaluated using the Menopausal Rating Scale (MRS) at four time points: before chemotherapy (T0), after the first (T1) and fourth (T2) cycles, and one month post-chemotherapy (T3). Symptom trajectories were analyzed using a linear mixed-effects model (LMM) and Generalized Estimating Equations (GEE). Results Menopausal symptoms significantly worsened in premenopausal women (AC-D: p < 0.001, FAC: p < 0.001), particularly from T2 onward. Psychological symptoms showed the greatest increase (AC-D: p < 0.001, FAC: p < 0.001), followed by significant worsening of urogenital symptoms (AC-D: p = 0.002, FAC: p = 0.004). Somatic symptoms showed a non-significant increasing trend (AC-D: p = 0.120, FAC: p = 0.101). At T3, 67.9% of AC-D and 59.4% of FAC patients experienced moderate-to-severe symptoms, with severe cases doubling in AC-D (from 16.1% at T0 to 37.5%) and tripling in FAC (6.8% at T0 to 18.9%). Conclusion Chemotherapy-induced menopausal symptoms progressively worsened, particularly psychological symptoms. By treatment completion, approximately two-thirds required clinical intervention, underscoring the need for early assessment and proactive management to improve patient outcomes.