Recombinant Human OBFC1
- Known as:
- Recombinant Human OBFC1
- Catalog number:
- CF99
- Product Quantity:
- 10ug
- Category:
- -
- Supplier:
- Novoprotein
- Gene target:
- Recombinant Human OBFC1
Related genes to: Recombinant Human OBFC1
- Gene:
- STN1 NIH gene
- Name:
- STN1 subunit of CST complex
- Previous symbol:
- OBFC1
- Synonyms:
- FLJ22559, bA541N10.2
- Chromosome:
- 10q24.33
- Locus Type:
- gene with protein product
- Date approved:
- 2004-03-16
- Date modifiied:
- 2019-01-25
Related products to: Recombinant Human OBFC1
Related articles to: Recombinant Human OBFC1
- Wnt/β-catenin signaling regulates oocyte development in vertebrates. However, the dynamics of Wnt/β-catenin signaling in oocyte progression remain unclear. Here, we analyze oocytes across different developmental stages in zebrafish and find that the activity of Wnt/β-catenin signaling sharply increases when oocytes reach a size of 10 to 45 μm (stage IA to middle stage IB) and subsequently declines rapidly. In addition, we show that expression of the CST complex subunit Stn1 is enriched in germ cells. Stn1 interacts with the transcription factor Tcf/Lef, facilitates its association with promoters of germ cell-specific genes, thereby enhancing Wnt/β-catenin signaling activity in oocytes. Genetic deletion of stn1 leads to massive loss of oocytes prior to or during their development to stage IB, resulting in a male-like phenotype associated with infertility. Temporal activation of the Wnt/β-catenin signaling pathway partially restores germ cell loss and facilitates oocyte development to stage IB. Our findings highlight the importance of Wnt/β-catenin signaling in promoting the expression of germ cell-specific genes and provide novel insights into the physiological function of Stn1 in maintaining oocyte development in zebrafish. - Source: PubMed
Publication date: 2026/04/17
Zhang XinZhai YanpengWang CaixiaHe YuxueHe YuxinWang BoHuang ChensongSheng AiboBai YanRong XiaozhiZhou Jianfeng - Replicative single-stranded DNA gaps are emerging as central intermediates in the cellular response to replication stress. Replication frequently continues past lesions or difficult-to-replicate regions through leading-strand repriming or delayed Okazaki fragment (OKF) maturation, generating structured gaps requiring stabilization and repair. Here, we describe the major routes of gap formation, including polymerase-helicase uncoupling, impaired OKF processing, PrimPol-mediated lesion bypass, and endogenous abasic site accumulation from base excision repair and DNA methylation turnover. We examine the mechanisms that suppress, protect, and resolve these gaps, highlighting RAD51/BRCA2-mediated stabilization, PCNA modifications, PARP1- and CTC1-STN1-TEN1 (CST)-dependent fill-in pathways, and the balance between translesion synthesis and template switching. Finally, we discuss how persistent gaps drive fork degradation, genome instability, and innate immune activation, contributing to explaining the therapeutic vulnerabilities and resistance of cancer cells to PARP, polymerase Q (Pol θ), and ATR inhibitors. This perspective presents a unified model in which timely replicative gap recognition and resolution ensure genome stability. - Source: PubMed
Publication date: 2026/03/20
Falbo LuciaCostanzo Vincenzo - Telomeres cap the extremities of linear chromosomes and prevent their detection as DNA damage. Telomere uncapping poses a profound threat to genome integrity, yet the immediate consequences of transient uncapping remain unclear. In Saccharomyces cerevisiae, the Cdc13-Stn1-Ten1 complex limits resection, preventing DNA damage checkpoint activation. Here, using the temperature-sensitive cdc13-1 allele, we demonstrate that transient telomere uncapping rapidly induces extensive genomic rearrangements despite a functional DNA damage checkpoint. Two distinct rearrangement signatures are observed in surviving cells: recombination of the subtelomeric region mostly involving the Y' elements, and massively elongated telomeres up to 10 kb, a ~ 30-fold increase. Long-read sequencing evidences Y' element losses/amplifications, terminal duplications, and telomeric-circle-driven amplifications of telomere repeats. Rearrangements unfold over multiple generations and require the homologous recombination factor Rad52, the Polδ subunit Pol32, and partially Rad51 and Rad59. Remarkably, survivors with elongated telomeres demonstrate a robust Rad52-dependent resistance to subsequent telomere uncapping. Our findings provide novel insights into the consequences of transient telomere uncapping for genome stability, a process that might contribute to subtelomere and telomere dynamics and evolution. - Source: PubMed
Publication date: 2026/02/17
Dudragne LiébautGarrido ClotildeIlioaia OanaBernardes Juliana SilvaXu Zhou - Maintaining telomere integrity is essential for cellular survival, and reactivation of telomerase or alternative lengthening of telomeres (ALT) represents a hallmark of cancer, ensuring replicative immortality. Osteosarcoma (OS), a malignancy in which many tumors rely on ALT for telomere maintenance, lacks effective therapeutic strategies targeting this pathway. This study aimed to identify and characterize novel molecular regulators of ALT activity and explore their potential as therapeutic targets in OS. Immunohistochemistry was performed to evaluate the expression of phosphorylated NPM1 (pT199-NPM1) in OS tissues. Functional experiments including NPM1 knockdown and rescue assays were conducted to assess the impact of NPM1 on break-induced telomere replication (BITR) and cell viability in ALT-positive cells. Mechanistic studies involving phosphorylation analysis, ubiquitination assays, and co-immunoprecipitation were used to determine how ATR-mediated phosphorylation of NPM1 regulates POLD3 stability and its interaction with the CST complex. Pharmacological screening was performed to identify compounds that inhibit ALT activity, followed by proliferation assays and mouse xenograft experiments to evaluate therapeutic efficacy and synergy with doxorubicin. We identified pT199-NPM1 as a novel, highly expressed protein factor in ALT-positive OS tissues. NPM1 depletion impaired break-induced telomere replication and significantly reduced the viability of ALT-positive cells. ATR signaling phosphorylated NPM1 at Thr199, which stabilized POLD3 by preventing its ubiquitin-mediated degradation. Recruitment and function of pT199-NPM1 at telomeric damage sites required STN1, defining a CST/pT199-NPM1/POLD3 regulatory axis essential for ALT activity. Clinically, elevated Thr199 phosphorylation correlated with poor survival in OS patients, while expression of a phosphorylation-deficient T199A mutant failed to sustain ALT telomere maintenance. Pharmacological screening identified EPZ-6438, an EZH2 inhibitor, as a potent ALT suppressor that reduced NPM1 transcription, inhibited homologous recombination-mediated telomere synthesis, and suppressed OS cell proliferation. In mouse xenografts, EPZ-6438 enhanced OS cell sensitivity to doxorubicin, suggesting therapeutic synergy. This study uncovers a novel CST/pT199-NPM1/POLD3 regulatory module that is critical for ALT telomere maintenance in OS. Targeting NPM1 or its downstream effectors effectively suppresses ALT activity and enhances chemotherapy response. These findings provide new mechanistic insights into telomere regulation in ALT-positive tumors and highlight the therapeutic potential of NPM1-centered pathways in OS. - Source: PubMed
Publication date: 2026/01/22
Zhao RuiLi TingfangYang QiuhuiJiang DuoXue YananKou HaomengWang QianqianWang YuwenHan XinyuMa WenbinWang GuowenFeng JinyanHan XiuxinLiu YanchengJing YaqingGeng XinWang FeiLiu YangZhang QiangWang Feng - CTCF/cohesin-binding sites (CBSs) at the chromatin-loop anchors and topologically associating domains are frequently mutated in cancer; however, the underlying molecular mechanisms remain unclear. Here, we investigate whether CTCF and cohesin co-binding on DNA imposes constraints on DNA replication, leading to DNA damage and genomic instability. Our results reveal that CTCF and cohesin remain co-bound to DNA during replication in cancer cells (HeLa). Furthermore, analysis of DNA damage response/repair (DDR) proteins-including MRE11, STN1, γH2AX, and RAD51-showed a high enrichment of these proteins at CBSs, compared with immediate flanking regions. The loss of DDR genes in tumor genomes showed a significant enrichment of somatic mutations at CBSs compared with those tumors with intact DDR genes. Together, we propose that CTCF and cohesin co-binding can impede replication fork progression, leading to DNA damage and DDR activation. However, in cells with defective DDR, these lesions may promote genomic instability at CBSs. - Source: PubMed
Publication date: 2026/01/08
Faseela Elangoli EbrahimkuttyNotani DimpleSabarinathan Radhakrishnan