Telomere Fusion(端粒融合)研究综述
Telomere Fusion 端粒融合 - Interestingly, the same exposure reduces the frequency of telomere fusions (TFs) from Drosophila telomere capping mutants suggesting that the LDDR can generally promote a protective response on chromatin sites that are recognized as DNA breaks. [1] Cell‐based model systems are designed with different strategies, such as the formation of nuclear structures called micronuclei, telomere fusions or the induction of exogenous DNA double‐strand breaks. [2] Telomere fusions lead to a state of genomic instability, and are thought to drive clonal evolution and tumorigenesis. [3] In Saccharomyces cerevisiae, dicentric chromosomes stemming from telomere fusions preferentially break at the fusion. [4] Effective DNA damage sensing and repair is integral to survival but is largely thought to occur primarily in interphase and be repressed during mitosis due to the risk of telomere fusion. [5] Furthermore, depletion of NCAPH2 results in a fragile telomere phenotype and apparent sister‐telomere fusions only days after NCAPH2 depletion. [6] Recent findings have established the presence of telomere fusions in human breast and prostate malignancies; however, the onset of this genomic instability mechanism during progression of other solid cancers is not well understood. [7] Telomere probes help to identify terminal deletion and telomere fusions. [8]有趣的是，相同的暴露降低了来自果蝇端粒加帽突变体的端粒融合 (TF) 的频率，这表明 LDDR 通常可以促进对被认为是 DNA 断裂的染色质位点的保护性反应。 [1] 基于细胞的模型系统采用不同的策略设计，例如形成称为微核的核结构、端粒融合或诱导外源 DNA 双链断裂。 [2] 端粒融合导致基因组不稳定状态，并被认为驱动克隆进化和肿瘤发生。 [3] 在酿酒酵母中，源自端粒融合的双着丝粒染色体优先在融合时断裂。 [4] 有效的 DNA 损伤感知和修复对于生存来说是不可或缺的，但在很大程度上被认为主要发生在间期，并且由于端粒融合的风险而在有丝分裂期间受到抑制。 [5] 此外，仅在 NCAPH2 耗尽后几天，NCAPH2 的消耗导致端粒表型脆弱和明显的姐妹端粒融合。 [6] 最近的研究结果已经确定在人类乳腺和前列腺恶性肿瘤中存在端粒融合。然而，在其他实体癌进展过程中这种基因组不稳定性机制的发生尚不清楚。 [7] 端粒探针有助于识别末端缺失和端粒融合。 [8]
Dependent Telomere Fusion
The SWSSS motif works redundantly with Lys242 SUMOylation to promote binding of Stn1-Ten1 at telomere and sub-telomere regions to protect against single-strand annealing (SSA)-dependent telomere fusions, and to prevent telomerase accumulation at telomeres. [1] The SWSSS motif works redundantly with Lys242 SUMOylation to promote binding of Stn1-Ten1 at telomere and sub-telomere regions to protect against single-strand annealing (SSA)-dependent telomere fusions, and to prevent telomerase accumulation at telomeres. [2]SWSSS 基序与 Lys242 SUMOylation 重复工作，以促进 Stn1-Ten1 在端粒和亚端粒区域的结合，以防止单链退火 (SSA) 依赖的端粒融合，并防止端粒酶在端粒积累。 [1] SWSSS 基序与 Lys242 SUMOylation 重复工作，以促进 Stn1-Ten1 在端粒和亚端粒区域的结合，以防止单链退火 (SSA) 依赖的端粒融合，并防止端粒酶在端粒积累。 [2]
Chromosomal Telomere Fusion
Progression through crisis was associated with abundant intra-chromosomal telomere fusions with increasing asymmetry and reduced microhomology usage, suggesting shifts in DNA repair capacity. [1] We have demonstrated the fundamental contribution of DNA ligase 4-dependent classical non-homologous end-joining to long-range inter-chromosomal telomere fusions. [2]危机的进展与丰富的染色体内端粒融合有关，不对称性增加和微同源使用减少，表明 DNA 修复能力发生了变化。 [1] 我们已经证明了 DNA 连接酶 4 依赖的经典非同源末端连接对长程染色体间端粒融合的基本贡献。 [2]
telomere fusion event
To investigate the impact of telomere dysfunction on the CLL genome, we performed a large-scale molecular characterisation of telomere fusion events in CLL B-cells. [1] Strikingly, removal of TPP1 and subsequent activation of ATR signaling rescued telomere fusion events in TRF2-depleted SMCHD1 knockout cells. [2]为了研究端粒功能障碍对 CLL 基因组的影响，我们对 CLL B 细胞中的端粒融合事件进行了大规模分子表征。 [1] 引人注目的是，TPP1 的去除和随后 ATR 信号的激活挽救了 TRF2 耗尽的 SMCHD1 敲除细胞中的端粒融合事件。 [2]