Zhao Qing-Guo, Lu Bai-Song, Huang Pei-Tang
Beijing Institute of Biotechnology, Beijing 100071, China.
Yi Chuan Xue Bao. 2005 Sep;32(9):993-1000.
Fanconi anemia (FA) is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure and cancer susceptibility. Cells from individuals with Fanconi anemia manifest features of spontaneous chromosomal instability and hypersensitivity to DNA cross-linking agents such as mitomycin C. Over 11 known Fanconi anemia gene products are involved in DNA damage response pathway. In the pathway, monoubiquitination of FANCD2 is a key step. A novel protein FANCL is a component of the nuclear FA complex, functioned as an ubiquitin E3 ligase and monoubiquitinylated FANCD2. FANCD2-Ub is targeted to chromatin, where it interacts with BRCA2 to repair DNA damage. In early embryo stage, FA pathway is probably involved in proliferation of PGCs. Mice deficient in FA proteins, such as FANCL, FANCC and FANCA, have a drastic reduction of primordial germ cells (PGC), resulting in male and female infertility in adult. In the adult male, FANCL and a few testis-specific proteins, GGN1 (gametogenetin protein 1), GGNBP1 (gametogenetin binding protein 1), GGNBP2 and OAZ3 (ornithine decarboxylase antizyme 3) form a novel testis-specific complex functioning in spermatogenesis. FANCL is involved in proliferation of PGCs in early embryo stage, and development of germ cells in adult.
范可尼贫血（FA）是一种罕见的常染色体隐性疾病，临床特征为先天性异常、进行性骨髓衰竭和癌症易感性。范可尼贫血患者的细胞表现出自发性染色体不稳定的特征，并且对丝裂霉素C等DNA交联剂高度敏感。超过11种已知的范可尼贫血基因产物参与DNA损伤反应途径。在该途径中，FANCD2的单泛素化是关键步骤。一种新的蛋白质FANCL是核FA复合物的组成部分，作为泛素E3连接酶发挥作用并使FANCD2单泛素化。FANCD2-Ub靶向染色质，在那里它与BRCA2相互作用以修复DNA损伤。在胚胎早期，FA途径可能参与原始生殖细胞（PGC）的增殖。缺乏FA蛋白（如FANCL、FANCC和FANCA）的小鼠，其原始生殖细胞（PGC）数量大幅减少，导致成年后雄性和雌性不育。在成年雄性中，FANCL与一些睾丸特异性蛋白，如GGN1（配子生成素蛋白1）、GGNBP1（配子生成素结合蛋白1）、GGNBP2和OAZ3（鸟氨酸脱羧酶抗酶3）形成一种新的睾丸特异性复合物，在精子发生中发挥作用。FANCL在胚胎早期参与PGC的增殖，在成年期参与生殖细胞的发育。
