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首页> 外文期刊>Genes to cells : >Xeroderma pigmentosum group F protein binds to Eg5 and is required for proper mitosis: implications for XP-F and XFE
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Xeroderma pigmentosum group F protein binds to Eg5 and is required for proper mitosis: implications for XP-F and XFE

机译：色皮干燥菌F组蛋白与Eg5结合，是适当的有丝分裂所必需的：对XP-F和XFE的影响

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摘要

The xeroderma pigmentosum group F-cross-complementing rodent repair deficiency group 1 (XPF-ERCC1) complex is a structure-specific endonuclease involved in nucleotide excision repair (NER) and interstrand cross-link (ICL) repair. Patients with XPF mutations may suffer from two forms of xeroderma pigmentosum (XP): XP-F patients show mild photosensitivity and proneness to skin cancer but rarely show any neurological abnormalities, whereas XFE patients display symptoms of severe XP symptoms, growth retardation and accelerated aging. Xpf knockout mice display accelerated aging and die before weaning. These results suggest that the XPF-ERCC1 complex has additional functions besides NER and ICL repair and is essential for development and growth. In this study, we show a partial colocalization of XPF with mitotic spindles and Eg5. XPF knockdown in cells led to an increase in the frequency of abnormal nuclear morphology and mitosis. Similarly, the frequency of abnormal nuclei and mitosis was increased in XP-F and XFE cells. In addition, we showed that Eg5 enhances the action of XPF-ERCC1 nuclease activity. Taken together, these results suggest that the interaction between XPF and Eg5 plays a role in mitosis and DNA repair and offer new insights into the pathogenesis of XP-F and XFE.
机译：色皮干燥症组F交叉互补啮齿动物修复缺陷组1（XPF-ERCC1）复合物是一种结构特异性核酸内切酶，参与核苷酸切除修复（NER）和链间交联（ICL）修复。 XPF突变的患者可能患有两种干性色素变性（XP）：XP-F患者表现出轻度的光敏性和易患皮肤癌，但很少表现出任何神经系统异常，而XFE患者表现出严重的XP症状，生长迟缓和加速衰老的症状。 Xpf基因敲除小鼠显示加速衰老并在断奶前死亡。这些结果表明，XPF-ERCC1复合物除了具有NER和ICL修复功能外，还具有其他功能，并且对于发育和增长至关重要。在这项研究中，我们显示XPF与有丝分裂纺锤体和Eg5的部分共定位。细胞中的XPF敲低导致异常核形态和有丝分裂的频率增加。同样，XP-F和XFE细胞中异常核和有丝分裂的频率也增加了。此外，我们表明Eg5增强XPF-ERCC1核酸酶活性的作用。两者合计，这些结果表明XPF和Eg5之间的相互作用在有丝分裂和DNA修复中起作用，并为XP-F和XFE的发病机理提供了新的见解。

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