Dedicated to the core: Understanding the Fanconi anemia complex
Dedicated to the core: Understanding the Fanconi anemia complex
复制标题
DOI：
10.1016/j.dnarep.2006.05.009
复制
发表时间：
2006-09-08
期刊：
影响因子：
3.8
通讯作者：
D'Andrea, Alan D.
中科院分区：
文献类型：
--
作者：
Gurtan, Allan M.;D'Andrea, Alan D.
范可尼贫血（FA）途径由独特的多亚基E3泛素连接酶复合物组成，其在复制和DNA损伤依赖性机制中被激活。该FA核心复合物具有推定的情况下，E3泛素连接酶亚基，在核质和染色质中组装，并且是遗传毒性应激后下游FA蛋白FANCD 2的单泛素化所需的。临床上，FA通路的缺失导致先天性缺陷、骨髓衰竭和癌症易感性。在细胞水平，该途径是染色体稳定性和细胞对DNA链间交联剂（ICL）如丝裂霉素C（MMC）的抗性所必需的。FA通路作为ICL后DNA损伤反应的一个分支，已经出现了一个通用模型。本文将总结目前对FA核心复合体的认识，并提出一个模型，其活动。(c)2006 Elsevier B.V.保留所有权利。
The Fanconi anemia (FA) pathway consists of a unique, multi-subunit E3 ubiquitin ligase complex that is activated in a replication and DNA-damage dependent mechanism. This FA core complex possesses a putative case an an E3 ubiquitin ligase subunit, is assembled in both the nucleoplasm and in chromatin, and is required for the mono-ubiquitination of FANCD2, a downstream FA protein, following genotoxic stress. Clinically, absence of the FA pathway results in congenital defects, bone marrow failure, and cancer predisposition. At the cellular level, this pathway is required for chromosomal stability and cellular resistance to DNA interstrand crosslinkers (ICLs) such as mitomycin C (MMC). A general model has emerged for the FA pathway as an arm of the DNA-damage response following ICLs. This review will summarize the current understanding of the FA core complex and propose a model for its activity. (c) 2006 Elsevier B.V. All rights reserved.