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控制染色体断裂修复途径之间的平衡。

Controlling the balance between chromosome break repair pathways.

机构信息

Departamento de Genética, Universidad de Sevilla, Sevilla, Spain; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla, Spain.

Departamento de Genética, Universidad de Sevilla, Sevilla, Spain; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla, Spain.

出版信息

Adv Protein Chem Struct Biol. 2019;115:95-134. doi: 10.1016/bs.apcsb.2018.10.004. Epub 2018 Dec 5.

Abstract

Broken chromosomes are among the most complex and more difficult to repair DNA lesions. The loss of the continuity of the DNA molecule presents a challenge to the cells, thus the repair of DNA double strand breaks might lead to genomic alterations. Indeed, to minimize this threat to genomic integrity, different DNA repair pathways can act on a broken chromosome. The balance between them is tightly controlled, and it heavily depends on global and local cellular cues. In this chapter, we review our current understanding on the repair of DNA double strand breaks and focus in the regulation of the balance between alternative pathways. Most of this modulation takes place at the level of DNA end resection. Here, we focus mostly on the local signals that control the repair pathway choice, as the global cues have been extensively reviewed recently. We described epigenetic marks that either facilitate or inhibit DNA resection and homologous recombination, from histone marks and chromatin remodelers to non-coding RNA and RNA-related factors.

摘要

断裂的染色体是最复杂和更难修复的 DNA 损伤之一。DNA 分子的连续性丧失给细胞带来了挑战,因此修复 DNA 双链断裂可能导致基因组改变。事实上,为了将这种对基因组完整性的威胁降到最低,不同的 DNA 修复途径可以作用于断裂的染色体。它们之间的平衡受到严格控制,并且严重依赖于全局和局部细胞线索。在本章中,我们回顾了我们对 DNA 双链断裂修复的现有理解,并重点介绍了替代途径之间平衡的调节。这种调节大部分发生在 DNA 末端切除水平。在这里,我们主要关注控制修复途径选择的局部信号,因为全局线索最近已被广泛综述。我们描述了从组蛋白标记和染色质重塑因子到非编码 RNA 和 RNA 相关因子等促进或抑制 DNA 切除和同源重组的表观遗传标记。

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