Mutation of the RAD51C gene in a Fanconi anemia-like disorder
Mutation of the RAD51C gene in a Fanconi anemia-like disorder
复制标题
DOI：
10.1038/ng.570
复制
发表时间：
2010-05-01
期刊：
影响因子：
30.8
通讯作者：
Mathew, Christopher G.
中科院分区：
文献类型：
--
作者：
Vaz, Fiona;Hanenberg, Helmut;Mathew, Christopher G.
范可尼贫血（FA）是一种罕见的染色体不稳定性疾病，与各种发育异常，骨髓衰竭和白血病和其他癌症的易感性有关（1）。我们已经确定了一个纯合错义突变的RAD 51 C基因在一个近亲家庭与多个严重的先天性异常的特点FA。RAD 51 C是参与同源重组介导的DNA修复的RAD 51样基因家族的成员。该突变导致响应于DNA损伤的RAD 51焦点形成的损失以及对DNA链间交联剂丝裂霉素C和拓扑异构酶-1抑制剂喜树碱的细胞敏感性增加。因此，RAD 51等位基因的生殖系突变与FA样综合征相关。
Fanconi anemia (FA) is a rare chromosomal-instability disorder associated with a variety of developmental abnormalities, bone marrow failure and predisposition to leukemia and other cancers(1). We have identified a homozygous missense mutation in the RAD51C gene in a consanguineous family with multiple severe congenital abnormalities characteristic of FA. RAD51C is a member of the RAD51-like gene family involved in homologous recombination-mediated DNA repair. The mutation results in loss of RAD51 focus formation in response to DNA damage and in increased cellular sensitivity to the DNA interstrand cross-linking agent mitomycin C and the topoisomerase-1 inhibitor camptothecin. Thus, biallelic germline mutations in a RAD51 paralog are associated with an FA-like syndrome.