Structure, function and evolution of the XPD family of iron-sulfur-containing 5′→3′ DNA helicases
Structure, function and evolution of the XPD family of iron-sulfur-containing 5′→3′ DNA helicases
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DOI：
10.1042/bst0370547
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发表时间：
2009-06-01
影响因子：
3.9
通讯作者：
White, Malcolm F.
中科院分区：
文献类型：
--
作者：
White, Malcolm F.
着色性干皮病(XPD)解旋酶家族由许多超家族2 DNA解旋酶组成，其成员广泛存在于生命的三个领域。其创始成员XPD解旋酶在古生物和真核生物中是保守的，而细菌中最接近的同源物是Ding(损伤诱导G)解旋酶。三个XPD类似物，FancJ(Fanconi‘s Anaia Componation Group J)，Rtel(规则端粒长度)和ChL1，已经在真核生物中进化，并在不同的DNA重组和修复途径中发挥作用。所有的家族成员都被认为是5‘->；3’DNA解旋酶，其结构包括一个重要的铁-硫簇结合域。最近的结构、突变和生物物理研究为XPD解旋酶的机制提供了一个分子框架，并有助于解释XPD基因相当数量的突变的表型，这些突变可以导致三种不同的遗传疾病：着色性干皮病、毛发硫代营养不良和Cockayne综合征。来自三种古生物的XPD的晶体结构显示出一个四个结构域的结构，其中包括两个典型的运动域和两个独特的结构域，称为Arch和铁-硫簇结合域。后两个结构域可能在解旋酶作用过程中协作分离双链DNA。讨论了铁-硫簇的作用和XPD解旋酶家族的进化。
The XPD (xeroderma pigmentosum complementation group D) helicase family comprises a number of superfamily 2 DNA helicases with members found in all three domains of life. The founding member, the XPD helicase, is conserved in archaea and eukaryotes, whereas the closest homologue in bacteria is the DinG (damage-inducible G) helicase. Three XPD paralogues, FancJ (Fanconi's anaemia complementation group J), RTEL (regular of telomere length) and Chl1, have evolved in eukaryotes and function in a variety of DNA recombination and repair pathways. All family members are believed to be 5'-> 3' DNA helicases with a structure that includes an essential iron-sulfur-cluster-binding domain. Recent structural, mutational and biophysical studies have provided a molecular framework for the mechanism of the XPD helicase and help to explain the phenotypes of a considerable number of mutations in the XPD gene that can cause three different genetic conditions: xeroderma pigmentosum, trichothiodystrophy and Cockayne's syndrome. Crystal structures of XPD from three archaeal organisms reveal a four-domain structure with two canonical motor domains and two unique domains, termed the Arch and iron-sulfur-cluster-binding domains. The latter two domains probably collaborate to separate duplex DNA during helicase action. The role of the iron-sulfur cluster and the evolution of the XPD helicase family are discussed.