Trypanosoma brucei harbours a divergent XPB helicase paralogue that is specialized in nucleotide excision repair and conserved among kinetoplastid organisms.

Trypanosoma brucei harbours a divergent XPB helicase paralogue that is specialized in nucleotide excision repair and conserved among kinetoplastid organisms.
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布氏锥虫拥有一种不同的 XPB 解旋酶旁系同源物,专门从事核苷酸切除修复并在动质体生物体中保守。

DOI:
10.1111/mmi.12435
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发表时间:
2013
影响因子:
3.6
通讯作者:
Günzl,Arthur
Günzl,Arthur
中科院分区:
生物学2区
文献类型:
--
作者:
Badjatia,Nitika;Nguyen,TuN;Lee,JuHuck;Günzl,Arthur

文献摘要

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从酵母到人类,TFIIH是RNA聚合酶II转录和核苷酸切除修复(NER)所必需的。TFIIH由DNA解旋酶、色素沉着病(XPB)和激酶亚复合物组成。布鲁氏锥虫itfiih包含所有核心复合物组分,是剪接先导RNA基因(slrna)的RNA聚合酶II转录所必需的。然而,着丝质体生物具有两个高度不同的XPB同源物,只有较大的一个被鉴定为TFIIH亚基。在这里,我们发现敲除较小的旁链基因,称为xpb‐R(R表示修复),导致培养的活锥虫生长速度比正常慢。XPB‐R的缺失对体内外转录没有影响,并且XPB‐R没有被发现占据组装RNA聚合酶II转录起始前复合物(包括TFIIH)的slrnapromoter。然而,与野生型细胞相比,XPB - R - / -细胞对紫外线和顺铂诱导的DNA损伤的耐受性要差得多,这需要NER。由于expb‐R−/−细胞在DNA碱基切除修复中没有受损,XPB‐R似乎在NER中特异性起作用。有趣的是,其他几个原生生物具有高度不同的XPB同源物,这表明在着丝质体之外存在专门从事转录或NER的XPB。
Conserved from yeast to humans, TFIIH is essential for RNA polymerase II transcription and nucleotide excision repair (NER). TFIIH consists of a core that includes the DNA helicaseXeroderma pigmentosumB (XPB) and a kinase subcomplex.Trypanosoma bruceiTFIIH harbours all core complex components and is indispensable for RNA polymerase II transcription of spliced leader RNA genes (SLRNAs). Kinetoplastid organisms, however, possess two highly divergent XPB paralogues with only the larger being identified as a TFIIH subunit inT. brucei. Here we show that a knockout of the gene for the smaller paralogue, termedXPB‐R(R for repair) resulted in viable cultured trypanosomes that grew slower than normal. XPB‐R depletion did not affect transcriptionin vivoorin vitroand XPB‐R was not found to occupy theSLRNApromoter which assembles a RNA polymerase II transcription pre‐initiation complex including TFIIH. However,XPB‐R−/−cells were much less tolerant than wild‐type cells to UV light‐ and cisplatin‐induced DNA damage, which require NER. SinceXPB‐R−/−cells were not impaired in DNA base excision repair, XPB‐R appears to function specifically in NER. Interestingly, several other protists possess highly divergent XPB paralogues suggesting that XPBs specialized in transcription or NER exist beyond the Kinetoplastida.