The Smc complexes in DNA damage response.

The Smc complexes in DNA damage response.
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DOI:
10.1186/2045-3701-2-5
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发表时间:
2012-02-27
期刊:
影响因子:
7.5
通讯作者:
Yu H
Yu H
中科院分区:
生物学2区
文献类型:
--
作者:
Wu N;Yu H

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染色体结构维持 (Smc) 蛋白几乎调节染色体生物学的所有方面,对于基因组稳定性至关重要。在真核生物中,六种 Smc 蛋白形成三个异二聚体——Smc1/3、Smc2/4 和 Smc5/6——它们与非 Smc 蛋白一起分别形成粘连蛋白、凝缩蛋白和 Smc5/6 复合物。正确的染色体分离需要粘连蛋白。它建立并维持姐妹染色单体的凝聚力,直到所有姐妹染色单体实现与有丝分裂纺锤体的双极附着。凝缩蛋白在有丝分裂过程中介导染色体凝缩。 Smc5/6 复合物在 DNA 修复中具有多种作用。除了在染色体凝聚和凝聚方面的主要功能外,黏连蛋白和凝聚蛋白还参与细胞 DNA 损伤反应。在这里,我们回顾了所有三种 Smc 复合物在 DNA 修复中的功能及其通过翻译后修饰(如乙酰化、磷酸化和苏酰化)调节细胞周期的最新进展。深入了解这些复合物促进 DNA 修复和基因组稳定性的机制可能有助于我们揭示人类癌症基因组不稳定性的分子基础,并设计利用这种不稳定性来治疗癌症的方法。
The structural maintenance of chromosomes (Smc) proteins regulate nearly all aspects of chromosome biology and are critical for genomic stability. In eukaryotes, six Smc proteins form three heterodimers--Smc1/3, Smc2/4, and Smc5/6--which together with non-Smc proteins form cohesin, condensin, and the Smc5/6 complex, respectively. Cohesin is required for proper chromosome segregation. It establishes and maintains sister-chromatid cohesion until all sister chromatids achieve bipolar attachment to the mitotic spindle. Condensin mediates chromosome condensation during mitosis. The Smc5/6 complex has multiple roles in DNA repair. In addition to their major functions in chromosome cohesion and condensation, cohesin and condensin also participate in the cellular DNA damage response. Here we review recent progress on the functions of all three Smc complexes in DNA repair and their cell cycle regulation by posttranslational modifications, such as acetylation, phosphorylation, and sumoylation. An in-depth understanding of the mechanisms by which these complexes promote DNA repair and genomic stability may help us to uncover the molecular basis of genomic instability in human cancers and devise ways that exploit this instability to treat cancers.
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