Coleman Kate E, Huang Tony T
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York NY, USA.
Front Genet. 2016 Apr 19;7:61. doi: 10.3389/fgene.2016.00061. eCollection 2016.
Fanconi anemia (FA) is a rare human genetic disorder characterized by developmental defects, bone marrow failure and cancer predisposition, primarily due to a deficiency in the repair of DNA interstrand crosslinks (ICLs). ICL repair through the FA DNA repair pathway is a complicated multi-step process, involving at least 19 FANC proteins and coordination of multiple DNA repair activities, including homologous recombination, nucleotide excision repair and translesion synthesis (TLS). SUMOylation is a critical regulator of several DNA repair pathways, however, the role of this modification in controlling the FA pathway is poorly understood. Here, we summarize recent advances in the fine-tuning of the FA pathway by small ubiquitin-like modifier (SUMO)-targeted ubiquitin ligases (STUbLs) and other SUMO-related interactions, and discuss the implications of these findings in the design of novel therapeutics for alleviating FA-associated condition, including cancer.
范可尼贫血（FA）是一种罕见的人类遗传疾病，其特征为发育缺陷、骨髓衰竭和癌症易感性，主要原因是DNA链间交联（ICL）修复缺陷。通过FA DNA修复途径进行的ICL修复是一个复杂的多步骤过程，涉及至少19种FANC蛋白以及多种DNA修复活动的协调，包括同源重组、核苷酸切除修复和跨损伤合成（TLS）。SUMO化是几种DNA修复途径的关键调节因子，然而，这种修饰在控制FA途径中的作用尚不清楚。在这里，我们总结了小泛素样修饰物（SUMO）靶向泛素连接酶（STUbL）和其他SUMO相关相互作用对FA途径进行微调的最新进展，并讨论了这些发现对设计缓解包括癌症在内的FA相关病症的新型疗法的意义。
