Fanconi anaemia (FA) is a hereditary disorder characterized by bone marrow failure, developmental defects, predisposition to cancer and chromosomal abnormalities. FA is caused by biallelic mutations that inactivate genes encoding proteins involved in replication stress-associated DNA damage responses. The 20 FANC proteins identified to date constitute the FANC pathway. A key event in this pathway involves the monoubiquitination of the FANCD2-FANCI heterodimer by the collective action of at least 10 different proteins assembled in the FANC core complex. The FANC core complex-mediated monoubiquitination of FANCD2-FANCI is essential to assemble the heterodimer in subnuclear, chromatin-associated, foci and to regulate the process of DNA repair as well as the rescue of stalled replication forks. Several recent works have demonstrated that the activity of the FANC pathway is linked to several other protein post-translational modifications from the ubiquitin-like family, including SUMO and NEDD8. These modifications are related to DNA damage responses but may also affect other cellular functions potentially related to the clinical phenotypes of the syndrome. This review summarizes the interplay between the ubiquitin and ubiquitin-like proteins and the FANC proteins that constitute a major pathway for the surveillance of the genomic integrity and addresses the implications of their interactions in maintaining genome stability.

中文翻译：

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遍在蛋白家族符合Fanconi贫血蛋白。

范可尼贫血（FA）是一种遗传性疾病，其特征是骨髓衰竭，发育缺陷，易患癌症和染色体异常。FA是由双等位基因突变引起的，该突变使编码与复制应激相关的DNA损伤反应中涉及的蛋白质的基因失活。迄今为止，鉴定出的20种FANC蛋白构成了FANC途径。该途径中的关键事件涉及FANCD2-FANCI异二聚体的单泛素化，这是通过在FANC核心复合物中装配的至少10种不同蛋白质的集体作用来实现的。FANCD2-FANCI的FANC核心复合物介导的单泛素化对于在核染色质相关的亚核中装配异源二聚体，调节DNA修复过程以及挽救停滞的复制叉至关重要。最近的一些研究表明，FANC途径的活性与遍在蛋白样家族的其他一些蛋白质翻译后修饰有关，包括SUMO和NEDD8。这些修饰与DNA损伤反应有关，但也可能影响可能与该综合征临床表型有关的其他细胞功能。这篇综述总结了泛素和泛素样蛋白与FANC蛋白之间的相互作用，这是监测基因组完整性的主要途径，并探讨了它们相互作用对维持基因组稳定性的影响。这些修饰与DNA损伤反应有关，但也可能影响可能与该综合征临床表型有关的其他细胞功能。这篇综述总结了泛素和泛素样蛋白与FANC蛋白之间的相互作用，这是监测基因组完整性的主要途径，并探讨了它们相互作用对维持基因组稳定性的影响。这些修饰与DNA损伤反应有关，但也可能影响可能与该综合征临床表型有关的其他细胞功能。这篇综述总结了泛素和泛素样蛋白与FANC蛋白之间的相互作用，这是监测基因组完整性的主要途径，并探讨了它们相互作用对维持基因组稳定性的影响。