The DNA repair helicases XPD and FancJ have essential iron-sulfur domains
The DNA repair helicases XPD and FancJ have essential iron-sulfur domains
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DOI：
10.1016/j.molcel.2006.07.019
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发表时间：
2006-09-15
期刊：
影响因子：
16
通讯作者：
White, Malcolm F.
中科院分区：
文献类型：
--
作者：
Rudolf, Jana;Makrantoni, Vasso;White, Malcolm F.
DNA 解旋酶是 DNA 复制、重组、修复和转录细胞机制的重要组成部分。 XPD 和 FancJ 蛋白是分别参与核苷酸切除修复 (NER) 和 Fanconi 贫血修复途径的相关解旋酶。我们证明这两种蛋白质在 N 末端附近都有一个保守结构域，其中包括铁硫 (Fe-S) 簇。三个绝对保守的半胱氨酸残基为 Fe-S 簇提供配体，这对于 XPD 的解旋酶活性至关重要。 Rad3 的 Fe-S 结构域（酵母 XPD）中含有突变的酵母菌株在 UV 光产物的切除修复中存在缺陷。毛发硫营养不良 (TTD) 和范可尼贫血患者的临床相关突变破坏了 XPD 和 FancJ 的 Fe-S 簇，从而消除了解旋酶活性。
DNA helicases are essential components of the cellular machinery for DNA replication, recombination, repair, and transcription. The XPD and FancJ proteins are related helicases involved in the nucleotide excision repair (NER) and Fanconi anemia repair pathways, respectively. We demonstrate that both proteins have a conserved domain near the N terminus that includes an iron-sulfur (Fe-S) cluster. Three absolutely conserved cysteine residues provide ligands for the Fe-S cluster, which is essential for the helicase activity of XPD. Yeast strains harboring mutations in the Fe-S domain of Rad3 (yeast XPD) are defective in excision repair of UV photoproducts. Clinically relevant mutations in patients with trichothiodystrophy (TTD) and Fanconi anemia disrupt the Fe-S clusters of XPD and FancJ and thereby abolish helicase activity.