Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, USA.
Mutat Res. 2011 Jul 1;712(1-2):20-7. doi: 10.1016/j.mrfmmm.2011.03.010. Epub 2011 Mar 30.
Fanconi anemia (FA) is a rare autosomal recessive disease characterized by bone marrow failure, developmental defects and cancer. There are multiple FA genes that enable the repair of interstrand crosslinks (ICLs) in coordination with a variety of other DNA repair pathways in a way that is poorly understood. Here we present the phenotype of mouse embryonic stem (ES) cells mutated for FancB. We found FancB-mutant cells exhibited reduced cellular proliferation, hypersensitivity to the crosslinking agent mitomycin C (MMC), increased spontaneous and MMC-induced chromosomal abnormalities, reduced spontaneous sister chromatid exchanges (SCEs), reduced gene targeting, reduced MMC-induced Rad51 foci and absent MMC-induced FancD2 foci. Since FancB is on the X chromosome and since ES cells are typically XY, FancB is an excellent target for an epistatic analysis to elucidate FA's role in ICL repair.
范可尼贫血症（FA）是一种罕见的常染色体隐性疾病，其特征为骨髓衰竭、发育缺陷和癌症。有多种 FA 基因能够与多种其他 DNA 修复途径协同修复链间交联（ICLs），但其机制尚不清楚。本文呈现了 FancB 基因突变的小鼠胚胎干细胞（ES 细胞）的表型。我们发现 FancB 突变细胞表现出细胞增殖减少、对交联剂丝裂霉素 C（MMC）的敏感性增加、自发和 MMC 诱导的染色体异常增加、自发姐妹染色单体交换（SCE）减少、基因靶向减少、MMC 诱导的 Rad51 焦点减少以及 MMC 诱导的 FancD2 焦点缺失。由于 FancB 位于 X 染色体上，而 ES 细胞通常为 XY，因此 FancB 是一个很好的上位性分析靶点，可阐明 FA 在 ICL 修复中的作用。
