Botanical Institute, Molecular Biology and Biochemistry, Karlsruhe Institute of Technology, Karlsruhe, Germany.
PLoS Genet. 2019 May 23;15(5):e1008174. doi: 10.1371/journal.pgen.1008174. eCollection 2019 May.
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.
范可尼贫血（FA）互补组的蛋白质是人类交联（CL）修复所必需的，其缺失会导致严重的病理表型。在这里，我们在模式植物拟南芥中鉴定了 FA 同源物 FANCJ 的同源物 AtFANCJB，并表明它参与了链间 CL 修复。它与核酸内切酶 FAN1 协同作用于假定的早期步骤，但独立于核酸内切酶 AtMUS81，并且与拟南芥中的易错和无差错复制后修复均呈上位性。FANCJB 和 Fe-S 簇螺旋酶 RTEL1 的同时敲除导致根分生组织中的诱导细胞死亡，表明这些酶在复制 DNA 修复中起着重要作用。令人惊讶的是，我们发现 AtFANCJB 参与植物中 rDNA 的稳定性。在缺乏 AtRTEL1 和 AtFANCJB 的情况下，我们检测到 45S rDNA 拷贝数减少到原来数量的三分之一左右。人们不禁推测，所检测到的 rDNA 不稳定性可能是由于 G-四链体结构分辨率的缺陷所致，因此可能导致某些人类遗传疾病的病理表型。
