端粒蛋白shelterin复合体影响肿瘤细胞基因组稳定性的研究进展
Research progress of effects of telomere protein shelterin complex on genomic stability of tumor cells
摘要端粒是真核生物线性染色体末端的帽状保护性结构,由双链DNA区和富含G碱基的3′突出端(单链DNA区)及端粒结合蛋白共同构成,是维持基因组稳定性的重要结构。端粒结合蛋白的核心成分,被称为shelterin复合体,可帮助端粒成帽,同时将端粒DNA隐藏于蛋白复合体间,免受DNA修复系统的识别,从而在形成端粒结构、保护染色体末端、维持基因组稳定等方面发挥重要作用。shelterin复合体组分的异常会导致端粒功能障碍及染色体末端融合或缺失,严重威胁基因组的稳定性,进而促进肿瘤的发生发展。作为基因组不稳定性的重要体现形式,双微体(double minute chromosomes,DMs)的形成与端粒的结构功能异常也存在相关性。本文总结了肿瘤细胞中shelterin复合体异常与基因组不稳定性的关联,试图阐明端粒蛋白参与的肿瘤恶性进展机制,为临床上改善恶性肿瘤预后提供新的靶点和思路。
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abstractsTelomere is a cap-like protective structure at the end of the linear chromosome of eukaryotes, which is composed of double-stranded DNA region, 3 ′ protrusion (single-stranded DNA region) rich in G base and telomere binding protein, and is an important structure to maintain genome stability.The core component of telomere binding protein, known as shelterin complex, can help telomeres become caps.At the same time, telomere DNA is hidden among protein complexes to avoid the identification of DNA repair system, which plays an important role in the formation of telomere structure, the protection of chromosome ends, and the maintenance of genome stability.The abnormality of shelterin complex components can lead to telomere dysfunction and chromosome end fusion or deletion, which seriously threatens the stability of the genome and promote the occurrence and development of tumors.As an important manifestation of genomic instability, the formation of double minute chromosomes knowledge about (DMs) is also related to the structural and functional abnormalities of telomeres.This paper summarizes the association between abnormal shelterin complex and genomic instability in tumor cells, and attempts to clarify the mechanism underlying malignant progression of tumors involving telomere proteins, so as to provide new targets and ideas for improving the prognosis of malignant tumors in clinic.
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