An Arabidopsis FANCJ helicase homologue is required for DNA crosslink repair and rDNA repeat stability
An Arabidopsis FANCJ helicase homologue is required for DNA crosslink repair and rDNA repeat stability
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DOI：
10.1371/journal.pgen.1008174
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发表时间：
2019-05-01
期刊：
影响因子：
4.5
通讯作者：
Puchta, Holger
中科院分区：
文献类型：
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作者：
Dorn, Annika;Feller, Laura;Puchta, Holger
Fanconi贫血（FA）互补组蛋白是人类交联（CL）修复所必需的，它们的缺失会导致严重的病理表型。在这里，我们描述了模式植物拟南芥中Fe-S簇解旋酶FANCJ的同源物AtFANCJB，并表明它参与了链间CL修复。它可能在早期与核酸酶FAN1协同作用，但独立于核酸酶AtMUS81，并且在拟南芥中易出错和无差错的复制后修复中都是显性的。同时敲除FANCJB和Fe-S簇解旋酶RTEL1导致根分生组织诱导细胞死亡，表明这些酶在复制性DNA修复中起重要作用。令人惊讶的是，我们发现AtFANCJB参与维护植物rDNA的稳定性。在缺少AtRTEL1和AtFANCJB的情况下，我们检测到45S rDNA拷贝数协同减少到原来的三分之一左右。我们很容易推测，检测到的rDNA不稳定性可能是由于g -四重体结构分辨率的缺陷，从而可能导致某些人类遗传疾病的病理表型。Fanconi贫血症和Hoyeraal-Hreidarsson综合征是与DNA修复缺陷相关的严重人类遗传性疾病。有趣的是，植物在其基因组中含有同源因子，这些同源因子在突变时导致各自的疾病。利用模式植物拟南芥，我们详细分析了两种解旋酶的作用，当人类有缺陷时，它们会导致一种或另一种综合征。我们发现，这两种解旋酶的同时缺失导致植物细胞对诱导和自然DNA损伤的协同缺陷，表明它们在不同的修复途径中起作用。最令人惊讶的是，我们发现在双重突变体中rDNA拷贝的急剧减少，这是核糖体形成和蛋白质合成所必需的。这种表型在人类和动物中都没有报道过，但这一发现可能显著地促进了各自疾病的特异性。
Proteins of the Fanconi Anemia (FA) complementation group are required for crosslink (CL) repair in humans and their loss leads to severe pathological phenotypes. Here we characterize a homolog of the Fe-S cluster helicase FANCJ in the model plant Arabidopsis, AtFANCJB, and show that it is involved in interstrand CL repair. It acts at a presumably early step in concert with the nuclease FAN1 but independently of the nuclease AtMUS81, and is epistatic to both error-prone and error-free post-replicative repair in Arabidopsis. The simultaneous knock out of FANCJB and the Fe-S cluster helicase RTEL1 leads to induced cell death in root meristems, indicating an important role of the enzymes in replicative DNA repair. Surprisingly, we found that AtFANCJB is involved in safeguarding rDNA stability in plants. In the absence of AtRTEL1 and AtFANCJB, we detected a synergetic reduction to about one third of the original number of 45S rDNA copies. It is tempting to speculate that the detected rDNA instability might be due to deficiencies in G-quadruplex structure resolution and might thus contribute to pathological phenotypes of certain human genetic diseases.Author summary The Fanconi Anemia and Hoyeraal-Hreidarsson syndromes are severe human genetic diseases that are correlated with DNA repair deficiencies. Interestingly, plants harbour homologues of factors in their genome that are causative for the respective diseases upon mutation. Using the model plant Arabidopsis, we analysed in detail the role of two helicases that are causing one or the other syndrome when defective in humans. We found that the simultaneous loss of both helicases leads to synergistic defects of plant cells in response to induced but also natural DNA damage, indicating that they act in different repair pathways. Most surprisingly, we found a drastic reduction of rDNA copies, in the double mutant, that are required for ribosome formation and thus protein synthesis. Such a phenotype has not been reported beforeneither for humans nor animalsbut this finding might significantly contribute to specificities of the respective diseases.