Fanconi anemia and the cell cycle: new perspectives on aneuploidy.
Fanconi anemia and the cell cycle: new perspectives on aneuploidy.
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DOI：
10.12703/p6-23
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Clapp DW
中科院分区：
文献类型：
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作者：
Nalepa G;Clapp DW
范可尼贫血（Fanconi anemia， FA）是一种复杂的异源性疾病，包括基因组不稳定、骨髓衰竭、癌症易感性和先天性畸形。FA信号网络协调着间期DNA损伤的识别和修复以及有丝分裂的正常进行。FA信号的丢失通过削弱纺锤体组装检查点、破坏中心体维护、干扰超细后期桥的分辨率和细胞分裂失调导致染色体不稳定。因此，FA基因在整个细胞周期中起着基因组稳定性守护者的作用。本文综述了范可尼贫血的诊断和临床治疗的最新进展，并对FA基因组不稳定性的起源提出了新的见解。这些新发现可能有助于制定合理的治疗策略，以治疗FA和普通人群中缺乏FA的恶性肿瘤。
Fanconi anemia (FA) is a complex heterogenic disorder of genomic instability, bone marrow failure, cancer predisposition, and congenital malformations. The FA signaling network orchestrates the DNA damage recognition and repair in interphase as well as proper execution of mitosis. Loss of FA signaling causes chromosome instability by weakening the spindle assembly checkpoint, disrupting centrosome maintenance, disturbing resolution of ultrafine anaphase bridges, and dysregulating cytokinesis. Thus, the FA genes function as guardians of genome stability throughout the cell cycle. This review discusses recent advances in diagnosis and clinical management of Fanconi anemia and presents the new insights into the origins of genomic instability in FA. These new discoveries may facilitate the development of rational therapeutic strategies for FA and for FA-deficient malignancies in the general population.