Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM
Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM
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DOI：
10.1016/j.molcel.2007.01.003
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发表时间：
2007-02-09
期刊：
影响因子：
16
通讯作者：
West, Stephen C.
中科院分区：
文献类型：
--
作者：
Ciccia, Alberto;Ling, Chen;West, Stephen C.
范科尼贫血（FA）核心复合物在与BRCA 1和BRCA 2的DNA损伤反应网络中发挥着至关重要的作用。这种复合物如何与受损的DNA相互作用尚不清楚，因为只有FA核心蛋白FANCM（古细菌解旋酶/核酸酶的同系物，称为HEF）具有DNA结合活性。在这里，我们描述了FAAP 24的鉴定，FAAP 24是一种将FANCM靶向模拟受损DNA复制/修复过程中形成的中间体的结构的蛋白质。FAAP 24与XPF家族的flap/fork内切核酸酶具有同源性，与FANCM的C-末端区域相关，并且是FA核心复合物的组分。FAAP 24是DNA损伤后FANCD 2单泛素化的正常水平所必需的。FAAP 24通过siRNA的消耗导致细胞对DNA交联剂的超敏性和染色体不稳定性。我们的数据表明，FANCM/FAAP 24复合物可能在FA核心复合物向受损DNA的募集中发挥关键作用。
The Fanconi anemia (FA) core complex plays a crucial role in a DNA damage response network with BRCA1 and BRCA2. How this complex interacts with damaged DNA is unknown, as only the FA core protein FANCM (the homolog of an archaeal helicase/nuclease known as HEF) exhibits DNA binding activity. Here, we describe the identification of FAAP24, a protein that targets FANCM to structures that mimic intermediates formed during the replication/repair of damaged DNA. FAAP24 shares homology with the XPF family of flap/fork endonucleases, associates with the C-terminal region of FANCM, and is a component of the FA core complex. FAAP24 is required for normal levels of FANCD2 monoubiquitylation following DNA damage. Depletion of FAAP24 by siRNA results in cellular hypersensitivity to DNA crosslinking agents and chromosomal instability. Our data indicate that the FANCM/FAAP24 complex may play a key role in recruitment of the FA core complex to damaged DNA.