Usher Syndrome Belongs to the Genetic Diseases Associated with Radiosensitivity: Influence of the ATM Protein Kinase.
Usher Syndrome Belongs to the Genetic Diseases Associated with Radiosensitivity: Influence of the ATM Protein Kinase.
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DOI：
10.3390/ijms23031570
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发表时间：
2022-01-29
影响因子：
5.6
通讯作者：
Foray N
中科院分区：
文献类型：
--
作者：
Al-Choboq J;Ferlazzo ML;Sonzogni L;Granzotto A;El-Nachef L;Maalouf M;Berthel E;Foray N
Usher综合征（USH）是一种罕见的常染色体隐性遗传病，其特征是听力丧失、视网膜色素变性引起的视力障碍，在某些情况下还包括前庭功能障碍。20世纪80年代发表的研究报告称，USH与细胞放射敏感性有关。然而，这种特殊表型的分子基础尚未被记录。因此，本研究的目的是通过检测来自USH1患者的三种皮肤成纤维细胞中辐射诱导的ATM （RIANS）核穿梭，以及DNA双链断裂（DSBs）的修复和信号通路的功能，来记录USH1 -一个USH1子集的辐射敏感性。克隆细胞存活、微核、H2A组蛋白X变体（H2AX）磷酸化形式形成的核灶、ATM蛋白（pATM）磷酸化形式和减数分裂重组11核酸酶（MRE11）作为细胞和分子终点。ATM和USH1蛋白之间的相互作用也通过邻近连接试验进行了检测。结果显示，USH1成纤维细胞具有中等但显著的放射敏感性、高微核产量和DSB识别受损，但DSB修复正常，可能是由RIANS延迟引起的，这表明细胞质中一些过表达的USH1蛋白可能会隔离ATM。据我们所知，该报告是第一个在分子和细胞尺度上对USH1患者细胞进行放射生物学表征的报告。
Usher syndrome (USH) is a rare autosomal recessive disease characterized by the combination of hearing loss, visual impairment due to retinitis pigmentosa, and in some cases vestibular dysfunctions. Studies published in the 1980s reported that USH is associated with cellular radiosensitivity. However, the molecular basis of this particular phenotype has not yet been documented. The aim of this study was therefore to document the radiosensitivity of USH1—a subset of USH—by examining the radiation-induced nucleo-shuttling of ATM (RIANS), as well as the functionality of the repair and signaling pathways of the DNA double-strand breaks (DSBs) in three skin fibroblasts derived from USH1 patients. The clonogenic cell survival, the micronuclei, the nuclear foci formed by the phosphorylated forms of the X variant of the H2A histone (ɣH2AX), the phosphorylated forms of the ATM protein (pATM), and the meiotic recombination 11 nuclease (MRE11) were used as cellular and molecular endpoints. The interaction between the ATM and USH1 proteins was also examined by proximity ligation assay. The results showed that USH1 fibroblasts were associated with moderate but significant radiosensitivity, high yield of micronuclei, and impaired DSB recognition but normal DSB repair, likely caused by a delayed RIANS, suggesting a possible sequestration of ATM by some USH1 proteins overexpressed in the cytoplasm. To our knowledge, this report is the first radiobiological characterization of cells from USH1 patients at both molecular and cellular scales.
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有丝分裂纺锤体蛋白Spag5/Astrin在森林膜上连接到Usher蛋白网络。
影响因子：
--
作者：
Kersten FF;van Wijk E;Hetterschijt L;Bauβ K;Peters TA;Aslanyan MG;van der Zwaag B;Wolfrum U;Keunen JE;Roepman R;Kremer H
通讯作者：
Kremer H
DOI：
10.1016/0360-3016(81)90377-1
发表时间：
1981-01-01
影响因子：
7
作者：
FERTIL, B;MALAISE, EP
通讯作者：
MALAISE, EP
影响因子：
2.6
作者：
Joubert, Aurelie;Zimmerman, Kristin M.;Foray, Nicolas
通讯作者：
Foray, Nicolas
影响因子：
3.5
作者：
Adato, A;Michel, V;Petit, C
通讯作者：
Petit, C
影响因子：
2
作者：
Lakhdar, Ismahane Moulay;Ferlazzo, Melanie L.;Foray, Nicolas
通讯作者：
Foray, Nicolas