Middle region of FancM interacts with Mhf and Rmi1 in silkworms, a species lacking the Fanconi anaemia (FA) core complex
Middle region of FancM interacts with Mhf and Rmi1 in silkworms, a species lacking the Fanconi anaemia (FA) core complex
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DOI：
10.1111/imb.12072
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发表时间：
2014-04-01
影响因子：
2.6
通讯作者：
Kusakabe, T.
中科院分区：
文献类型：
--
作者：
Sugahara, R.;Mon, H.;Kusakabe, T.
Fanconi贫血(FA)途径负责链间交联(ICL)的修复。在FA核心复合体成分中，FANCM被认为是ICL阻断的复制叉的损伤传感器，也是FA核心复合体组装和与Bloom综合征(BS)复合体相互作用的分子平台，后者被认为在处理DNA结构(如停滞的复制叉)中发挥重要作用。在本研究中，我们发现在家蚕中，缺乏主要FA核心复合体成分(FANCA、B、C、E、F和G)的家蚕，在丝裂霉素C(MMC)存在下，FANCD2的单偶联素化和细胞增殖需要FancM。家蚕FancM(BmFancM)在中间区域被磷酸化，这种修饰与其亚细胞定位有关。此外，BmFancM与组蛋白折叠蛋白Mhf1和BS复合体的亚基Rmi1在不同区域相互作用。至少包含这两个蛋白结合区的相互作用区域在FancM依赖的MMC耐药中发挥了重要作用。我们的结果表明，BmFancM也是FA蛋白和BS蛋白招募的平台，尽管家蚕基因组似乎失去了FAAP24，FAAP24是哺乳动物中FancM结合的伙伴蛋白。
The Fanconi anaemia (FA) pathway is responsible for interstrand crosslink (ICL) repair. Among the FA core complex components, FANCM is believed to act as a damage sensor for the ICL-blocked replication fork and also as a molecular platform for FA core complex assembly and interaction with Bloom's syndrome (BS) complex that is thought to play an important role in the processing of DNA structures such as stalled replication forks. In the present study, we found that in silkworms, Bombyx mori, a species lacking the major FA core complex components (FANCA, B, C, E, F, and G), FancM is required for FancD2 monoubiquitination and cell proliferation in the presence of mitomycin C (MMC). Silkworm FancM (BmFancM) was phosphorylated in the middle regions, and the modification was associated with its subcellular localization. In addition, BmFancM interacted with Mhf1, a histone-fold protein, and Rmi1, a subunit of the BS complex, in the different regions. The interaction region containing at least these two protein-binding domains played an essential role in FancM-dependent resistance to MMC. Our results suggest that BmFancM also acts as a platform for recruitment of both the FA protein and the BS protein, although the silkworm genome seems to lose FAAP24, a FancM-binding partner protein in mammals.