Recruitment of fanconi anemia and breast cancer proteins to DNA damage sites is differentially governed by replication.
Recruitment of fanconi anemia and breast cancer proteins to DNA damage sites is differentially governed by replication.
复制标题
DOI：
10.1016/j.molcel.2009.06.034
复制
发表时间：
2009-09-11
期刊：
影响因子：
16
通讯作者：
Li, Lei
中科院分区：
文献类型：
--
作者：
Shen, Xi;Do, Huong;Li, Yongjiang;Chung, Woo-Hyun;Tomasz, Maria;de Winter, Johan P.;Xia, Bing;Elledge, Stephen J.;Wang, Weidong;Li, Lei
范可尼贫血 (FA) 的特点是细胞对 DNA 交联剂过敏，但范可尼途径如何保护细胞免受 DNA 交联以及 FA 蛋白是否直接作用于交联仍不清楚。我们开发了一种基于染色质 IP 的策略，称为 eChIP，并检测了多种 FA 蛋白与体内 DNA 交联的关联。相互依赖性分析表明，各种 FA 蛋白的交联特异性富集是由不同的机制控制的。 BRCA 相关 FA 蛋白（BRCA2、FANCJ/BACH1 和 FANCN/PALB2）（但 FA 核心和 I/D2 复合物除外）需要复制才能实现其交联关联。 FANCD2（而非 FANCJ 和 FANCN）需要 FA 核心复合体来进行招募。 FA 核心复合物需要核苷酸切除修复蛋白 XPA 和 XPC 才能结合。与独特的招募机制一致，与 BRCA 相关 FA 蛋白相比，缺乏 FANC 核心的细胞中不依赖于重组的交联修复受到相反影响。因此，FA 蛋白参与受 DNA 复制状态控制的不同 DNA 损伤反应机制。
Fanconi anemia (FA) is characterized by cellular hypersensivity to DNA crosslinking agents, but how the Fanconi pathway protects cells from DNA crosslinks and whether FA proteins act directly on crosslinks remains unclear. We developed a chromatin-IP-based strategy termed eChIP and detected association of multiple FA proteins with DNA crosslinks in vivo. Inter-dependence analyses revealed that crosslink-specific enrichment of various FA proteins is controlled by distinct mechanisms. BRCA-related FA proteins (BRCA2, FANCJ/BACH1, and FANCN/PALB2), but not FA core and I/D2 complexes, require replication for their crosslink association. FANCD2, but not FANCJ and FANCN, requires the FA core complex for its recruitment. FA core complex requires nucleotide excision repair proteins XPA and XPC for its association. Consistent with the distinct recruitment mechanism, recombination-independent crosslink repair was inversely affected in cells deficient of FANC-core versus BRCA-related FA proteins. Thus, FA proteins participate in distinct DNA damage response mechanisms governed by DNA replication status.
登录
查看更多内容
影响因子：
20.3
作者：
Wagner, JE;Tolar, J;Auerbach, AD
通讯作者：
Auerbach, AD
影响因子：
16
作者：
Ciccia, Alberto;Ling, Chen;West, Stephen C.
通讯作者：
West, Stephen C.
影响因子：
16
作者：
Matsushita, N;Kitao, H;Takata, M
通讯作者：
Takata, M
影响因子：
64.8
作者：
Erkko, Hannele;Xia, Bing;Winqvist, Robert
通讯作者：
Winqvist, Robert
影响因子：
5.4
作者：
Wensing, B;Stühler, A;Farrell, PJ
通讯作者：
Farrell, PJ