Mutations of the SLX4 gene in Fanconi anemia.
Mutations of the SLX4 gene in Fanconi anemia.
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DOI：
10.1038/ng.750
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发表时间：
2011-02
期刊：
影响因子：
30.8
通讯作者：
Smogorzewska, Agata
中科院分区：
文献类型：
--
作者：
Kim, Yonghwan;Lach, Francis P.;Desetty, Rohini;Hanenberg, Helmut;Auerbach, Arleen D.;Smogorzewska, Agata
范可尼贫血是一种罕见的隐性遗传性疾病，其特征是基因组不稳定、先天性畸形、进行性骨髓衰竭以及易患血液系统恶性肿瘤和实体瘤。在细胞水平上，对DNA链间交联的超敏反应是范可尼贫血的定义特征。十三个不同的范可尼贫血基因的突变已被证明干扰DNA复制依赖性修复病变涉及交联DNA在停滞的复制叉。SLX 4与多种核酸酶相互作用，最近被鉴定为霍利迪连接消退酶，，，，导致细胞对DNA交联剂的敏感性增加。在此，我们报告了在两个具有典型的范可尼贫血临床特征的个体中鉴定出双等位基因SLX 4突变，并表明这些个体细胞中的细胞缺陷被野生型SLX 4补充，从而证明SLX 4中的双等位基因突变（在此重新命名为FANCP）导致范可尼贫血的新亚型，范可尼贫血-P。
Fanconi anemia is a rare recessive disorder characterized by genome instability, congenital malformations, progressive bone marrow failure and predisposition to hematologic malignancies and solid tumors. At the cellular level, hypersensitivity to DNA interstrand crosslinks is the defining feature in Fanconi anemia. Mutations in thirteen distinct Fanconi anemia genes have been shown to interfere with the DNA-replication–dependent repair of lesions involving crosslinked DNA at stalled replication forks. Depletion of SLX4, which interacts with multiple nucleases and has been recently identified as a Holliday junction resolvase,,, results in increased sensitivity of the cells to DNA crosslinking agents. Here we report the identification of biallelicSLX4mutations in two individuals with typical clinical features of Fanconi anemia and show that the cellular defects in these individuals' cells are complemented by wildtype SLX4, demonstrating that biallelic mutations inSLX4(renamed here asFANCP) cause a new subtype of Fanconi anemia, Fanconi anemia-P.
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影响因子：
64.5
作者：
Fekairi S;Scaglione S;Chahwan C;Taylor ER;Tissier A;Coulon S;Dong MQ;Ruse C;Yates JR 3rd;Russell P;Fuchs RP;McGowan CH;Gaillard PHL
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Gaillard PHL
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64.8
作者：
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STRATTON, MR
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64.5
作者：
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通讯作者：
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30.8
作者：
Vaz, Fiona;Hanenberg, Helmut;Mathew, Christopher G.
通讯作者：
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