DNA triplexes and Friedreich ataxia.
DNA triplexes and Friedreich ataxia.
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DNA 三链体和弗里德赖希共济失调。
DOI：
10.1096/fj.07-097857
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
Wells,RobertD
中科院分区：
文献类型：
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作者：
Wells,RobertD
弗里德赖希共济失调是遗传性共济失调中最常见的一种，由FXN基因的转录沉默引起，FXN基因编码210个氨基酸的共济失调蛋白，这是一种参与铁硫簇生物合成的线粒体蛋白。内含子1中的GAATTC序列扩展到多达1700个重复序列，通过形成非B DNA结构（三链体或粘性DNA）、形成持久的DNA-RNA杂交体或异染色质形成来消除转录沉默。长重复序列所采用的三链体（粘性DNA）也导致了突变、遗传不稳定性和重组行为。涉及聚酰胺或组蛋白脱乙酰酶抑制剂的早期治疗研究正在进行中。弗里德赖希共济失调可能是从病理生理学角度研究最彻底的遗传性神经疾病之一。威尔斯河D. DNA triplexes and Friedreich ataxia.FASEB J.22，1625-1634（2008）
Friedreich ataxia, the most common in herited ataxia, is caused by the transcriptional silencing of the FXN gene, which codes for the 210 amino acid frataxin, a mitochondrial protein involved in iron‐ sulfur cluster biosynthesis. The expansion of the GAATTC tract in intron 1 to as many as 1700 repeats elicits the transcriptional silencing by the formation of non‐B DNA structures (triplexes or sticky DNA), the formation of a persistent DNA‐RNA hybrid, or hetero chromatin formation. The triplex (sticky DNA) adopted by the long repeat sequence also elicits pro found mutagenic, genetic instability, and recombination behaviors. Early stage therapeutic investigations involving polyamides or histone deacetylase inhibitors are being pursued. Friedreich ataxia may be one of the most thoroughly studied hereditary neurological dis ease from a pathophysiological standpoint.— Wells, R. D. DNA triplexes and Friedreich ataxia.FASEB J.22, 1625–1634 (2008)