1Q12 Loci Movement in the Interphase Nucleus Under the Action of ROS Is an Important Component of the Mechanism That Determines Copy Number Variation of Satellite III (1q12) in Health and Schizophrenia

ROS 作用下的间期核中 1Q12 基因座运动是决定健康和精神分裂症中卫星 III (1q12) 拷贝数变异机制的重要组成部分

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作者:Marina Sergeevna Konkova, Elizaveta Sergeevna Ershova, Ekaterina Alekseevna Savinova, Elena Mikhailovna Malinovskaya, Galina Vasilievna Shmarina, Andrey Vladimirovich Martynov, Roman Vladimirovich Veiko, Nataly Vyacheslavovna Zakharova, Pavel Umriukhin, Georgy Petrovich Kostyuk, Vera Leonidovna Izhe

Conclusion

When a cell population responds to stress, cells are selected according to the size of the 1q12 domain (the f-SatIII content). The low content of the f-SatIII repeat in SZ patients may be a consequence of the chronic oxidative stress and of a large copies number of the ribosomal repeats.

Methods

2D fluorescent in situ hybridization (FISH) method was used for the satellite III fragment from the 1q12 region (f-SatIII) localization analysis in the interphase nuclei of healthy control (HC) lymphocytes, schizophrenia (SZ) patients, and in cultured mesenchymal stem cells (MSCs). The localization of the nucleolus was analyzed by the nucleolus Ag staining. The non-radioactive quantitative hybridization (NQH) technique was used for the f-SatIII fragment content in DNA analysis. Satellite III fragments transcription was analyzed by reverse transcriptase quantitative PCR (RT-qPCR).

Results

Low-dose IR induces the small-area 1q12 domains movement from the periphery to the central regions of the nucleus in HC lymphocytes and MSCs. Simultaneously, nucleolus moves from the nucleus center toward the nuclear envelope. The nucleolus in that period increases. The distance between the 1q12 domain and the nucleolus in irradiated cells is significantly reduced. The large-area 1q12 domains do not move in response to stress. During prolonged cultivation, the irradiated cells with a large f-SatIII amount die, and the population is enriched with the cells with low f-SatIII content. IR induces satellite III transcription in HC lymphocytes. Intact SZ patients' lymphocytes have the same signs of nuclei activation as irradiated HC cells.

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