Conserved XPB core structure and motifs for DNA unwinding: Implications for pathway selection of transcription or excision repair
Conserved XPB core structure and motifs for DNA unwinding: Implications for pathway selection of transcription or excision repair
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DOI：
10.1016/j.molcel.2006.02.017
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发表时间：
2006-04-07
期刊：
影响因子：
16
通讯作者：
Tainer, JA
中科院分区：
文献类型：
--
作者：
Fan, L;Arvai, AS;Tainer, JA
人着色性干皮病B组（XPB）解旋酶对于转录、核苷酸切除修复和TFIIH功能组装是必需的。在这里，我们确定了一个闪烁古生菌XPB同源物（AfXPB）的晶体结构，其特征在于两个RecA样XPB解旋酶结构域，并发现了一个DNA损伤识别结构域（DRD），一个独特的RED基序，一个灵活的拇指基序（ThM），并暗示了保守的功能核心内的构象变化。RED基序突变显着降低解旋酶活性，并且位于RED基序侧翼的DRD和ThM在结构和功能上似乎与MutS错配识别和DNA聚合酶拇指结构域类似。底物特异性被DNA损伤改变，使得AfXPB解旋具有3 '延伸的dsDNA，但不解旋平端dsDNA，除非它含有损伤，如CPD或（6-4）光产物所示。总之，这些结果提供了一种意想不到的DNA解旋机制，并对核苷酸切除修复中的XPB损伤验证产生影响。
The human xeroderma pigmentosum group B (XPB) helicase is essential for transcription, nucleotide excision repair, and TFIIH functional assembly. Here, we determined crystal structures of an Archaeoglobus fulgidus XPB homolog (AfXPB) that characterize two RecA-like XPB helicase domains and discover a DNA damage recognition domain (DRD), a unique RED motif, a flexible thumb motif (ThM), and implied conformational changes within a conserved functional core. RED motif mutations dramatically reduce helicase activity, and the DRD and ThM, which flank the RED motif, appear structurally as well as functionally analogous to the MutS mismatch recognition and DNA polymerase thumb domains. Substrate specificity is altered by DNA damage, such that AfXPB unwinds dsDNA with 3'extensions, but not blunt-ended dsDNA, unless it contains a lesion, as shown for CPD or (6-4) photoproducts. Together, these results provide an unexpected mechanism of DNA unwinding with implications for XPB damage verification in nucleotide excision repair.