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The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control.

机译:NBS1在DNA双链断裂修复,端粒稳定性和细胞周期检查点控制中的作用。

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摘要

The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. Failure of the DNA damage response can lead to development of malignancy by reducing the efficiency and fidelity of DNA repair. The NBS1 protein is a component of the MRE11/RAD50/NBS1 complex (MRN) that plays a critical role in the cellular response to DNA damage and the maintenance of chromosomal integrity. Mutations in the NBS1 gene are responsible for Nijmegen breakage syndrome (NBS), a hereditary disorder that imparts an increased predisposition to development of malignancy. The phenotypic characteristics of cells isolated from NBS patients point to a deficiency in the repair of DNA double strand breaks. Here, we review the current knowledge of the role of NBS1 in the DNA damage response. Emphasis is placed on the role of NBS1 in the DNA double strand repair, modulation of the DNA damage sensing and signaling, cell cycle checkpoint control and maintenance of telomere stability.Cell Research (2006) 16: 45-54. doi:10.1038/sj.cr.7310007; published online 16 January 2006.
机译:真核细胞的基因组受到环境因素和内源性代谢副产物的不断攻击。 DNA诱导的损伤通常导致一系列细胞事件,即DNA损伤反应。 DNA损伤反应的失败可通过降低DNA修复的效率和保真度而导致恶性肿瘤的发展。 NBS1蛋白是MRE11 / RAD50 / NBS1复合物(MRN)的组成部分,在细胞对DNA损伤的反应和维持染色体完整性中起着关键作用。 NBS1基因的突变是奈梅亨断裂综合症(NBS)的原因,后者是一种遗传性疾病,易患恶性肿瘤。从NBS患者中分离出的细胞的表型特征表明DNA双链断裂修复的缺陷。在这里,我们回顾了有关NBS1在DNA损伤反应中的作用的当前知识。重点放在NBS1在DNA双链修复,DNA损伤传感和信号转导的调控,细胞周期检查点控制和端粒稳定性维持中的作用。CellResearch(2006)16:45-54。 doi:10.1038 / sj.cr.7310007;在线发布于2006年1月16日。

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