文章：

范可尼贫血/BRCA途径

The Fanconi anaemia/BRCA pathway

原文发布日期：2003-01-01

DOI: 10.1038/nrc970

类型: Review Article

开放获取: 否

要点：

1. Fanconi anaemia (FA) is an autosomal recessive disease that is characterized by developmental abnormalities, cancer susceptibility and cellular sensitivity to crosslinking agents.
2. The seven cloned FA proteins interact in a common pathway. Five FA proteins (A, C, E, F and G) regulate the activation, via monoubiquitylation, of FANCD2.
3. Activated FANCD2 is targeted to BRCA1 nuclear foci. The FANCD1 gene is BRCA2.
4. The FA/BRCA pathway seems to regulate DNA repair by homologous recombination.
5. Ionizing radiation activates the ATM-dependent phosphorylation of FANCD2, resulting in an intra-S checkpoint response.
6. FANCD2 interacts with the MRE11–NBS1–RAD50 complex in the repair of DNA crosslinks.
7. Somatic inactivation of the FA/BRCA pathway accounts for the chromosomal instability of some cancers in the general population.
8. Mouse models for FA subtypes A, C, D1, D2 and G have been generated.
9. DNA crosslink repair, which is defective in cells from FA patients, requires S-phase arrest and homologous recombination repair.

要点翻译：

1. 范可尼贫血（FA）是一种常染色体隐性遗传病，其特征包括发育异常、癌症易感性以及细胞对交联剂的敏感性。
2. 七个已克隆的FA蛋白通过共同通路相互作用，其中五个FA蛋白（A、C、E、F和G）通过单泛素化调节FANCD2的激活。
3. 激活后的FANCD2会定位至BRCA1核焦点，而FANCD1基因即为BRCA2。
4. FA/BRCA通路似乎通过同源重组机制调控DNA修复。
5. 电离辐射通过ATM依赖性磷酸化激活FANCD2，从而引发S期内检查点反应。
6. FANCD2与MRE11–NBS1–RAD50复合物协同作用修复DNA交联。
7. FA/BRCA通路的体细胞失活是普通人群中某些癌症染色体不稳定的原因。
8. 目前已建立FA亚型A、C、D1、D2和G的小鼠模型。
9. FA患者细胞中存在缺陷的DNA交联修复过程需要S期阻滞和同源重组修复共同参与。

英文摘要：

Fanconi anaemia (FA) is a rare genetic cancer-susceptibility syndrome that is characterized by congenital abnormalities, bone-marrow failure and cellular sensitivity to DNA crosslinking agents. Seven FA-associated genes have recently been cloned, and their products were found to interact with well-known DNA-damage-response proteins, including BRCA1, ATM and NBS1. The FA proteins could therefore be involved in the cell-cycle checkpoint and DNA-repair pathways. Recent studies implicate the FA proteins in the process of repairing chromosome defects that occur during homologous recombination, and disruption of the FA genes results in chromosome instability — a common feature of many human cancers.

摘要翻译： 

范可尼贫血（FA）是一种罕见的遗传性癌症易感综合征，其特征为先天性畸形、骨髓衰竭以及对DNA交联剂的细胞敏感性。近期已克隆出七个FA相关基因，其产物被发现与著名的DNA损伤应答蛋白（包括BRCA1、ATM和NBS1）相互作用。因此，FA蛋白可能参与细胞周期检查点和DNA修复途径。最新研究提示，FA蛋白参与修复同源重组过程中出现的染色体缺陷，而FA基因的破坏会导致染色体不稳定性——这是许多人类癌症的共有特征。

原文链接：

The Fanconi anaemia/BRCA pathway