Chenyi Zhong, Huiyuan Wang, Xiong Yuan, Yuheng He, Jing Cong, Rui Yang, Wenjie Ma, Li Gao, Chao Gao, Yugui Cui, Jie Wu, Rongrong Tan, Danhua Pu
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引用次数: 0
Abstract
Background: Helicase for meiosis 1 (HFM1), a putative DNA helicase expressed in germ-line cells, has been reported to be closely associated with premature ovarian insufficiency (POI). However, the underlying molecular mechanism has not been clearly elucidated. The aim of this study was to investigate the function of HFM1 in the first meiotic prophase of mouse oocytes.
Results: The results suggested that the deficiency of HFM1 resulting in increased apoptosis and depletion of oocytes in mice, while the oocytes were arrested in the pachytene stage of the first meiotic prophase. In addition, impaired DNA double-strand break repair and disrupted synapsis were observed in the absence of HFM1. Further investigation revealed that knockout of HFM1 promoted ubiquitination and degradation of FUS protein mediated by FBXW11. Additionally, the depletion of HFM1 altered the intranuclear localization of FUS and regulated meiotic- and oocyte development-related genes in oocytes by modulating the expression of BRCA1.
Conclusions: These findings elaborated that the critical role of HFM1 in orchestrating the regulation of DNA double-strand break repair and synapsis to ensure meiosis procession and primordial follicle formation. This study provided insights into the pathogenesis of POI and highlighted the importance of HFM1 in maintaining proper meiotic function in mouse oocytes.
背景:减数分裂螺旋酶 1(HFM1)是一种在生殖细胞中表达的推定 DNA 螺旋酶,据报道与卵巢早衰(POI)密切相关。然而,其潜在的分子机制尚未明确阐明。本研究旨在探讨HFM1在小鼠卵母细胞减数第一次分裂前期的功能:结果:结果表明,HFM1的缺乏导致小鼠卵母细胞凋亡和耗竭增加,同时卵母细胞停滞在减数第一次分裂前期的pachytene阶段。此外,在 HFM1 缺失的情况下,还观察到 DNA 双链断裂修复受损和突触中断。进一步研究发现,HFM1的敲除促进了FUS蛋白在FBXW11介导下的泛素化和降解。此外,HFM1的缺失改变了FUS的核内定位,并通过调节BRCA1的表达调控卵母细胞中减数分裂和卵母细胞发育相关基因:这些发现阐明了HFM1在协调DNA双链断裂修复和突触调控中的关键作用,从而确保减数分裂过程和原始卵泡的形成。这项研究揭示了 POI 的发病机制,并强调了 HFM1 在维持小鼠卵母细胞正常减数分裂功能方面的重要性。
期刊介绍:
Biological Research is an open access, peer-reviewed journal that encompasses diverse fields of experimental biology, such as biochemistry, bioinformatics, biotechnology, cell biology, cancer, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology and systems biology.